Galectin-3: Endozytose und Recycling in polaren Epithelzellen sowie seine Rolle im klarzelligen Nierenzellkarzinom

Polare Epithelzellen stellen die Voraussetzung für ein funktionierendes Organ, wie z.B die Niere, dar. Sie bilden ein Monolayer an der Organaußenseite, das als Barriere gegen die Umwelt fungiert aber auch als Austauschsystem mit der Umwelt dient. Die polarisierte Struktur einer Epithelzelle ist d...

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Main Author: Straube, Tamara
Contributors: Jacob, Ralf (Prof.) (Thesis advisor)
Format: Dissertation
Language:German
Published: Philipps-Universität Marburg 2014
Klinische Zytobiologie und Zytopathologie
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1. Laemmli, U.K., 1970, Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.


2. Wehrle-Haller, B., Imhof, B.A., 2001, Stem cell factor presentation to c-Kit. Identification of a basolateral targeting domain. J Biol Chem 276, 12667- 12674.


3. Pralle, A., Keller, P., Florin, E.L., Simons, K., Horber, J.K., 2000, Sphingolipid- cholesterol rafts diffuse as small entities in the plasma membrane of mammalian cells. J Cell Biol 148, 997-1008.


4. Wolf, A.A., Jobling, M.G., Wimer-Mackin, S., Ferguson-Maltzman, M., Madara, J.L., Holmes, R.K., Lencer, W.I., 1998, Ganglioside structure dictates signal transduction by cholera toxin and association with caveolae-like membrane domains in polarized epithelia. J Cell Biol 141, 917-927.


5. Yamashiro, D.J., Maxfield, F.R., 1987, Acidification of morphologically distinct endosomes in mutant and wild-type Chinese hamster ovary cells. J Cell Biol 105, 2723-2733.


6. Kurzchalia, T.V., Dupree, P., Parton, R.G., Kellner, R., Virta, H., Lehnert, M., Simons, K., 1992, VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network-derived transport vesicles. J Cell Biol 118, 1003-1014.


7. Sjoblom, T., Jones, S., Wood, L.D., Parsons, D.W., Lin, J., Barber, T.D., Mandelker, D., Leary, R.J., Ptak, J., Silliman, N., Szabo, S., Buckhaults, P., Farrell, C., Meeh, P., Markowitz, S.D., Willis, J., Dawson, D., Willson, J.K., Gazdar, A.F., Hartigan, J., Wu, L., Liu, C., Parmigiani, G., Park, B.H., Bachman, K.E., Papadopoulos, N., Vogelstein, B., Kinzler, K.W., Velculescu, V.E., 2006, The consensus coding sequences of human breast and colorectal cancers. Science 314, 268-274.


8. Nickel, W., 2005, Unconventional secretory routes: direct protein export across the plasma membrane of mammalian cells. Traffic 6, 607-614.


9. Wang, S., Luo, Y., Wilson, P.D., Witman, G.B., Zhou, J., 2004, The autosomal recessive polycystic kidney disease protein is localized to primary cilia, with concentration in the basal body area. J Am Soc Nephrol 15, 592- 602.


10. Winyard, P.J., Bao, Q., Hughes, R.C., Woolf, A.S., 1997, Epithelial galectin-3 during human nephrogenesis and childhood cystic diseases. J Am Soc Nephrol 8, 1647-1657.


11. Kobayashi, T., Shimura, T., Yajima, T., Kubo, N., Araki, K., Tsutsumi, S., Suzuki, H., Kuwano, H., Raz, A., 2011, Transient gene silencing of galectin-3 suppresses pancreatic cancer cell migration and invasion through degradation of beta-catenin. Int J Cancer 129, 2775-2786.


12. Svenberg, T., 1976, Carcinoembryonic antigen-like substances of human bile. Isolation and partial characterization. Int J Cancer 17, 588-596.


13. Tani, T., Laitinen, L., Kangas, L., Lehto, V.P., Virtanen, I., 1995, Expression of E-and N-cadherin in renal cell carcinomas, in renal cell carcinoma cell lines in vitro and in their xenografts. Int J Cancer 64, 407-414.


14. Salisbury, J.L., 2007, A mechanistic view on the evolutionary origin for centrin- based control of centriole duplication. J Cell Physiol 213, 420-428.


15. Yu, J., Fischman, D.A., Steck, T.L., 1973, Selective solubilization of proteins and phospholipids from red blood cell membranes by nonionic detergents. J Supramol Struct 1, 233-248.


16. Openo, K.P., Kadrofske, M.M., Patterson, R.J., Wang, J.L., 2000, Galectin-3 expression and subcellular localization in senescent human fibroblasts. Exp Cell Res 255, 278-290.


17. Ivanov, A.I., 2008, Pharmacological inhibition of endocytic pathways: is it specific enough to be useful? Methods Mol Biol 440, 15-33.


18. Storkel, S., 1999, [Epithelial tumors of the kidney. Pathological subtyping and cytogenetic correlation]. Urologe A 38, 425-432.


19. Merseburger, A.S., Kramer, M.W., Hennenlotter, J., Serth, J., Kruck, S., Gracia, A., Stenzl, A., Kuczyk, M.A., 2008a, Loss of galectin-3 expression correlates with clear cell renal carcinoma progression and reduced survival. World J Urol 26, 637-642.


20. Nio, J., Takahashi-Iwanaga, H., Morimatsu, M., Kon, Y., Iwanaga, T., 2006, Immunohistochemical and in situ hybridization analysis of galectin-3, a beta-galactoside binding lectin, in the urinary system of adult mice. Histochem Cell Biol 126, 45-56.


21. Takata, K., Matsuzaki, T., Tajika, Y., Ablimit, A., Hasegawa, T., 2008, Localization and trafficking of aquaporin 2 in the kidney. Histochem Cell Biol 130, 197-209.


22. Lutz, N.W., Franks, S.E., Frank, M.H., Pomer, S., Hull, W.E., 2005, Investigation of multidrug resistance in cultured human renal cell carcinoma cells by 31P-NMR spectroscopy and treatment survival assays. MAGMA 18, 144-161.


23. Nakahara, S., Oka, N., Raz, A., 2005, On the role of galectin-3 in cancer apoptosis. Apoptosis 10, 267-275.


24. Lukyanov, P., Furtak, V., Ochieng, J., 2005, Galectin-3 interacts with membrane lipids and penetrates the lipid bilayer. Biochem Biophys Res Commun 338, 1031-1036.


25. Perret, E., Lakkaraju, A., Deborde, S., Schreiner, R., Rodriguez-Boulan, E., 2005, Evolving endosomes: how many varieties and why? Curr Opin Cell Biol 17, 423-434.


26. Waguri, S., Tomiyama, Y., Ikeda, H., Hida, T., Sakai, N., Taniike, M., Ebisu, S., Uchiyama, Y., 2006, The luminal domain participates in the endosomal trafficking of the cation-independent mannose 6-phosphate receptor. Exp Cell Res 312, 4090-4107.


27. Yang, R.Y., Rabinovich, G.A., Liu, F.T., 2008, Galectins: structure, function and therapeutic potential. Expert Rev Mol Med 10, e17.


28. Nittka, S., Gunther, J., Ebisch, C., Erbersdobler, A., Neumaier, M., 2004, The human tumor suppressor CEACAM1 modulates apoptosis and is implicated in early colorectal tumorigenesis. Oncogene 23, 9306-9313.


29. Song, S., Byrd, J.C., Mazurek, N., Liu, K., Koo, J.S., Bresalier, R.S., 2005, Galectin-3 modulates MUC2 mucin expression in human colon cancer cells at the level of transcription via AP-1 activation. Gastroenterology 129, 1581-1591.


30. Kim, S.J., Choi, I.J., Cheong, T.C., Lee, S.J., Lotan, R., Park, S.H., Chun, K.H., 2010, Galectin-3 increases gastric cancer cell motility by up-regulating fascin-1 expression. Gastroenterology 138, 1035-1045 e1031-1032.


31. Jacob, R., Preuss, U., Panzer, P., Alfalah, M., Quack, S., Roth, M.G., Naim, H., Naim, H.Y., 1999, Hierarchy of sorting signals in chimeras of intestinal lactase-phlorizin hydrolase and the influenza virus hemagglutinin. J Biol Chem 274, 8061-8067.


32. Martin-Belmonte, F., Arvan, P., Alonso, M.A., 2001, MAL mediates apical transport of secretory proteins in polarized epithelial Madin-Darby canine kidney cells. J Biol Chem 276, 49337-49342.


33. Wolf, A.A., Fujinaga, Y., Lencer, W.I., 2002, Uncoupling of the cholera toxin- G(M1) ganglioside receptor complex from endocytosis, retrograde Golgi trafficking, and downstream signal transduction by depletion of membrane cholesterol. J Biol Chem 277, 16249-16256.


34. Kokkonen, N., Rivinoja, A., Kauppila, A., Suokas, M., Kellokumpu, I., Kellokumpu, S., 2004, Defective acidification of intracellular organelles results in aberrant secretion of cathepsin D in cancer cells. J Biol Chem 279, 39982-39988.


35. Kilic, N., Oliveira-Ferrer, L., Wurmbach, J.H., Loges, S., Chalajour, F., Neshat- Vahid, S., Weil, J., Fernando, M., Ergun, S., 2005, Pro-angiogenic signaling by the endothelial presence of CEACAM1. J Biol Chem 280, 2361-2369.


36. Nakahara, S., Hogan, V., Inohara, H., Raz, A., 2006, Importin-mediated nuclear translocation of galectin-3. J Biol Chem 281, 39649-39659.


37. Ito, K., Yoshii, H., Asakuma, J., Sato, A., Horiguchi, A., Sumitomo, M., Hayakawa, M., Asano, T., 2009, Clinical impact of the presence of the worst nucleolar grade in renal cell carcinoma specimens. Jpn J Clin Oncol 39, 588-594.


38. Maher, E.R., Yates, J.R., Harries, R., Benjamin, C., Harris, R., Moore, A.T., Ferguson-Smith, M.A., 1990, Clinical features and natural history of von Hippel-Lindau disease. Q J Med 77, 1151-1163.


39. Shimazui, T., Bringuier, P.P., van Berkel, H., Ruijter, E., Akaza, H., Debruyne, F.M., Oosterwijk, E., Schalken, J.A., 1997, Decreased expression of alpha-catenin is associated with poor prognosis of patients with localized renal cell carcinoma. Int J Cancer 74, 523-528.


40. Mays, R.W., Nelson, W.J., Marrs, J.A., 1995, Generation of epithelial cell polarity: roles for protein trafficking, membrane-cytoskeleton, and E- cadherin-mediated cell adhesion. Cold Spring Harb Symp Quant Biol 60, 763-773.


41. Singla, V., Reiter, J.F., 2006, The primary cilium as the cell's antenna: signaling at a sensory organelle. Science 313, 629-633.


42. Pante, N., Aebi, U., 1996, Sequential binding of import ligands to distinct nucleopore regions during their nuclear import. Science 273, 1729-1732.


43. Shimura, T., Takenaka, Y., Fukumori, T., Tsutsumi, S., Okada, K., Hogan, V., Kikuchi, A., Kuwano, H., Raz, A., 2005, Implication of galectin-3 in Wnt signaling. Cancer Res 65, 3535-3537.


44. Lutz, M.S., Burk, R.D., 2006, Primary cilium formation requires von hippel- lindau gene function in renal-derived cells. Cancer Res 66, 6903-6907.


45. Song, S., Mazurek, N., Liu, C., Sun, Y., Ding, Q.Q., Liu, K., Hung, M.C., Bresalier, R.S., 2009, Galectin-3 mediates nuclear beta-catenin accumulation and Wnt signaling in human colon cancer cells by regulation of glycogen synthase kinase-3beta activity. Cancer Res 69, 1343-1349.


46. Riethdorf, L., Lisboa, B.W., Henkel, U., Naumann, M., Wagener, C., Loning, T., 1997, Differential expression of CD66a (BGP), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland. J Histochem Cytochem 45, 957-963.


47. Thies, A., Moll, I., Berger, J., Wagener, C., Brummer, J., Schulze, H.J., Brunner, G., Schumacher, U., 2002, CEACAM1 expression in cutaneous malignant melanoma predicts the development of metastatic disease. J Clin Oncol 20, 2530-2536.


48. Sundberg, U., Beauchemin, N., Obrink, B., 2004, The cytoplasmic domain of CEACAM1-L controls its lateral localization and the organization of desmosomes in polarized epithelial cells. J Cell Sci 117, 1091-1104.


49. Schuck, S., Simons, K., 2004, Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane. J Cell Sci 117, 5955-5964.


50. Zink, S., Grosse, L., Freikamp, A., Banfer, S., Muksch, F., Jacob, R., 2012, Tubulin detyrosination promotes monolayer formation and apical trafficking in epithelial cells. J Cell Sci 125, 5998-6008.


51. Mackay, B., Ordonez, N.G., Khoursand, J., Bennington, J.L., 1987, The ultrastructure and immunocytochemistry of renal cell carcinoma. Ultrastruct Pathol 11, 483-502.


52. Markel, G., Lieberman, N., Katz, G., Arnon, T.I., Lotem, M., Drize, O., Blumberg, R.S., Bar-Haim, E., Mader, R., Eisenbach, L., Mandelboim, O., 2002, CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity. J Immunol 168, 2803-2810.


53. Nigg, E.A., 2006, Origins and consequences of centrosome aberrations in human cancers. Int J Cancer 119, 2717-2723.


54. Margadant, C., Monsuur, H.N., Norman, J.C., Sonnenberg, A., 2011, Mechanisms of integrin activation and trafficking. Curr Opin Cell Biol 23, 607-614.


55. Pilarsky, C., Koch-Brandt, C., 1992, Acidification slows the transport but does not influence the polarity of secretion of gp80 in the polarized epithelial cell MDCK. Eur J Cell Biol 59, 275-279.


56. Parczyk, K., Kondor-Koch, C., 1989, The influence of pH on the vesicular traffic to the surface of the polarized epithelial cell, MDCK. Eur J Cell Biol 48, 353-359.


57. Warfield, P.R., Makker, P.N., Raz, A., Ochieng, J., 1997, Adhesion of human breast carcinoma to extracellular matrix proteins is modulated by galectin-3. Invasion Metastasis 17, 101-112.


58. Nouwen, E.J., Dauwe, S., van der Biest, I., De Broe, M.E., 1993, Stage-and segment-specific expression of cell-adhesion molecules N-CAM, A-CAM, and L-CAM in the kidney. Kidney Int 44, 147-158.


59. Mans, D.A., Voest, E.E., Giles, R.H., 2008, All along the watchtower: is the cilium a tumor suppressor organelle? Biochim Biophys Acta 1786, 114- 125.


60. Yeaman, C., Le Gall, A.H., Baldwin, A.N., Monlauzeur, L., Le Bivic, A., Rodriguez-Boulan, E., 1997, The O-glycosylated stalk domain is required for apical sorting of neurotrophin receptors in polarized MDCK cells. J Cell Biol 139, 929-940.


61. Piepenhagen, P.A., Nelson, W.J., 1993, Defining E-cadherin-associated protein complexes in epithelial cells: plakoglobin, beta-and gamma-catenin are distinct components. J Cell Sci 104 ( Pt 3), 751-762.


62. Laoukili, J., Perret, E., Middendorp, S., Houcine, O., Guennou, C., Marano, F., Bornens, M., Tournier, F., 2000, Differential expression and cellular distribution of centrin isoforms during human ciliated cell differentiation in vitro. J Cell Sci 113 ( Pt 8), 1355-1364.


63. Spector, D.L., 2001, Nuclear domains. J Cell Sci 114, 2891-2893.


64. Mehul, B., Hughes, R.C., 1997, Plasma membrane targetting, vesicular budding and release of galectin 3 from the cytoplasm of mammalian cells during secretion. J Cell Sci 110 ( Pt 10), 1169-1178.


65. Weisz, O.A., Rodriguez-Boulan, E., 2009, Apical trafficking in epithelial cells: signals, clusters and motors. J Cell Sci 122, 4253-4266.


66. Sakaki, M., Fukumori, T., Fukawa, T., Elsamman, E., Shiirevnyamba, A., Nakatsuji, H., Kanayama, H.O., 2010, Clinical significance of Galectin-3 in clear cell renal cell carcinoma. J Med Invest 57, 152-157.


67. Kundu, A., Avalos, R.T., Sanderson, C.M., Nayak, D.P., 1996, Transmembrane domain of influenza virus neuraminidase, a type II protein, possesses an apical sorting signal in polarized MDCK cells. J Virol 70, 6508-6515.


68. Sambrook, J., Fritsch, E., Maniatis, T.P., und Russel, D.W., 2001, Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press 3.


69. Talamini, R., Baron, A.E., Barra, S., Bidoli, E., La Vecchia, C., Negri, E., Serraino, D., Franceschi, S., 1990, A case-control study of risk factor for renal cell cancer in northern Italy. Cancer Causes Control 1, 125-131.


70. Natoli, C., Dianzani, F., Mazzotta, F., Balocchini, E., Pierotti, P., Antonelli, G., Iacobelli, S., 1993, 90K protein: a new predictor marker of disease progression in human immunodeficiency virus infection. J Acquir Immune Defic Syndr 6, 370-375.


71. Matlin, K.S., 1986, Ammonium chloride slows transport of the influenza virus hemagglutinin but does not cause mis-sorting in a polarized epithelial cell line. J Biol Chem 261, 15172-15178.


72. Neumaier, M., Paululat, S., Chan, A., Matthaes, P., Wagener, C., 1993, Biliary glycoprotein, a potential human cell adhesion molecule, is down- regulated in colorectal carcinomas. Proc Natl Acad Sci U S A 90, 10744- 10748.


73. Prall, F., Nollau, P., Neumaier, M., Haubeck, H.D., Drzeniek, Z., Helmchen, U., Loning, T., Wagener, C., 1996, CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is expressed in epithelium, Literaturverzeichnis S e i t e | 211


74. Skubitz, K.M., Ducker, T.P., Goueli, S.A., 1992, CD66 monoclonal antibodies recognize a phosphotyrosine-containing protein bearing a carcinoembryonic antigen cross-reacting antigen on the surface of human neutrophils. J Immunol 148, 852-860.


75. Tilki, D., Singer, B.B., Shariat, S.F., Behrend, A., Fernando, M., Irmak, S., Buchner, A., Hooper, A.T., Stief, C.G., Reich, O., Ergun, S., 2010, CEACAM1: a novel urinary marker for bladder cancer detection. Eur Urol 57, 648-654.


76. Straube T., Elli A., Greb C., Hegele A., Elsässer HP., Delacour D. und Jacob R. (2011). Changes in the expression and subcellular distribution of galectin- 3 in clear cell renal cell carcinoma. J Exp Clin Cancer Res


77. Yu, M.C., Mack, T.M., Hanisch, R., Cicioni, C., Henderson, B.E., 1986, Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma. J Natl Cancer Inst 77, 351-356.


78. Thoenes, W., Rumpelt, H.J., Storkel, S., 1990, [Classification of renal cell carcinoma/tumors and their relationship to the nephron-collecting tubules system]. Klin Wochenschr 68, 1102-1111.


79. Wang, J.L., Sun, S.Z., Qu, X., Liu, W.J., Wang, Y.Y., Lv, C.X., Sun, J.Z., Ma, R., 2011, Clinicopathological significance of CEACAM1 gene expression in breast cancer. Chin J Physiol 54, 332-338.


80. Koths, K., Taylor, E., Halenbeck, R., Casipit, C., Wang, A., 1993, Cloning and characterization of a human Mac-2-binding protein, a new member of the superfamily defined by the macrophage scavenger receptor cysteine-rich domain. J Biol Chem 268, 14245-14249.


81. Lapierre, L.A., Ducharme, N.A., Drake, K.R., Goldenring, J.R., Kenworthy, A.K., 2012, Coordinated regulation of caveolin-1 and Rab11a in apical Lisanti, M.P., Le Bivic, A., Sargiacomo, M., Rodriguez-Boulan, E., 1989b, Steady-state distribution and biogenesis of endogenous Madin-Darby canine kidney glycoproteins: evidence for intracellular sorting and polarized cell surface delivery. J Cell Biol 109, 2117-2127.


82. Correlated Expression of Galectin-3 with the tumour supressor gene CEACAM1 in human clear cell renal cell carcinoma. Manuskript in


83. Lotz, M.M., Andrews, C.W., Jr., Korzelius, C.A., Lee, E.C., Steele, G.D., Jr., Clarke, A., Mercurio, A.M., 1993, Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma. Proc Natl Acad Sci U S A 90, 3466-3470.


84. Menon, R.P., Hughes, R.C., 1999, Determinants in the N-terminal domains of galectin-3 for secretion by a novel pathway circumventing the endoplasmic reticulum-Golgi complex. Eur J Biochem 264, 569-576.


85. Mareel, M., Vleminckx, K., Vermeulen, S., Bracke, M., Van Roy, F., 1992, E- cadherin expression: a counterbalance for cancer cell invasion. Bull Cancer 79, 347-355.


86. Sienel, W., Dango, S., Woelfle, U., Morresi-Hauf, A., Wagener, C., Brummer, J., Mutschler, W., Passlick, B., Pantel, K., 2003, Elevated expression of carcinoembryonic antigen-related cell adhesion molecule 1 promotes Literaturverzeichnis S e i t e | 213 progression of non-small cell lung cancer. Clin Cancer Res 9, 2260- 2266.


87. Straube T., Bänfer S., Jacob R., (2013). Endocytosis of Galectin-3 by 3D GSDIM. Manuskript in Vorbereitung


88. endothelium, and myeloid cells in a wide range of normal human tissues.


89. Johnson, D., Lanahan, A., Buck, C.R., Sehgal, A., Morgan, C., Mercer, E., Bothwell, M., Chao, M., 1986, Expression and structure of the human NGF receptor. Cell 47, 545-554.


90. Ochieng, J., Furtak, V., Lukyanov, P., 2004, Extracellular functions of galectin-3. Glycoconj J 19, 527-535.


91. Shimura, T., Takenaka, Y., Tsutsumi, S., Hogan, V., Kikuchi, A., Raz, A., 2004, Galectin-3, a novel binding partner of beta-catenin. Cancer Res 64, 6363-6367.


92. O'Driscoll, L., Linehan, R., Liang, Y.H., Joyce, H., Oglesby, I., Clynes, M., 2002, Galectin-3 expression alters adhesion, motility and invasion in a lung cell line (DLKP), in vitro. Anticancer Res 22, 3117-3125.


93. Waalkes, S., Merseburger, A.S., Simon, A., Serth, J., Kuczyk, M.A., 2010, [Galectin expression in urological cancer. Diagnostic, prognostic and therapeutic potential]. Urologe A 49, 387-391.


94. Oka, N., Takenaka, Y., Raz, A., 2004, Galectins and urological cancer. J Cell Biochem 91, 118-124.


95. Liu, F.T., Rabinovich, G.A., 2005, Galectins as modulators of tumour progression. Nat Rev Cancer 5, 29-41.


96. Syrjanen, K., Hjelt, L., 1978, Grading of human renal adenocarcinoma. Scand J Urol Nephrol 12, 49-55.


97. Ross, M.H., 2007, Histology, a text and atlas: with correlated cell and molecular biology. Lippincott Williams & Wilkins.


98. Oikawa, S., Kuroki, M., Matsuoka, Y., Kosaki, G., Nakazato, H., 1992, Homotypic and heterotypic Ca(++)-independent cell adhesion activities of biliary glycoprotein, a member of carcinoembryonic antigen family, expressed on CHO cell surface. Biochem Biophys Res Commun 186, 881-887.


99. Vila, M.R., Nicolas, A., Morote, J., de, I., Meseguer, A., 2000, Increased glyceraldehyde-3-phosphate dehydrogenase expression in renal cell carcinoma identified by RNA-based, arbitrarily primed polymerase chain reaction. Cancer 89, 152-164.


100. Jacobson, K., Mouritsen, O.G., Anderson, R.G., 2007, Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 9, 7-14.


101. Meyer-Siegler, K.L., Iczkowski, K.A., Vera, P.L., 2006, Macrophage migration inhibitory factor is increased in the urine of patients with urinary tract infection: macrophage migration inhibitory factor-protein complexes in human urine. J Urol 175, 1523-1528.


102. Khaldoyanidi, S.K., Glinsky, V.V., Sikora, L., Glinskii, A.B., Mossine, V.V., Quinn, T.P., Glinsky, G.V., Sriramarao, P., 2003, MDA-MB-435 human breast carcinoma cell homo-and heterotypic adhesion under flow conditions is mediated in part by Thomsen-Friedenreich antigen-galectin- 3 interactions. J Biol Chem 278, 4127-4134.


103. White, J., Kielian, M., Helenius, A., 1983, Membrane fusion proteins of enveloped animal viruses. Q Rev Biophys 16, 151-195.


104. Parczyk, K., Haase, W., Kondor-Koch, C., 1989, Microtubules are involved in the secretion of proteins at the apical cell surface of the polarized epithelial cell, Madin-Darby canine kidney. J Biol Chem 264, 16837- 16846.


105. Wendland, M., Waheed, A., von Figura, K., Pohlmann, R., 1991, Mr 46,000 mannose 6-phosphate receptor. The role of histidine and arginine residues for binding of ligand. J Biol Chem 266, 2917-2923.


106. Keller, P., Toomre, D., Diaz, E., White, J., Simons, K., 2001, Multicolour imaging of post-Golgi sorting and trafficking in live cells. Nat Cell Biol 3, 140-149.


107. Tsukita, S., Furuse, M., Itoh, M., 2001, Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2, 285-293.


108. Sparrow, C.P., Leffler, H., Barondes, S.H., 1987, Multiple soluble beta- galactoside-binding lectins from human lung. J Biol Chem 262, 7383- 7390.


109. Matera, A.G., 1999, Nuclear bodies: multifaceted subdomains of the interchromatin space. Trends Cell Biol 9, 302-309.


110. Rohatgi, R., Milenkovic, L., Scott, M.P., 2007, Patched1 regulates hedgehog signaling at the primary cilium. Science 317, 372-376.


111. Nauli, S.M., Zhou, J., 2004, Polycystins and mechanosensation in renal and nodal cilia. Bioessays 26, 844-856.


112. Partridge, E.A., Le Roy, C., Di Guglielmo, G.M., Pawling, J., Cheung, P., Granovsky, M., Nabi, I.R., Wrana, J.L., Dennis, J.W., 2004, Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science 306, 120-124.


113. Pace, K.E., Lee, C., Stewart, P.L., Baum, L.G., 1999, Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1. J Immunol 163, 3801-3811.


114. Karagiannis, T.C., El-Osta, A., 2005, RNA interference and potential therapeutic applications of short interfering RNAs. Cancer Gene Ther 12, 787-795.


115. Yang, R.Y., Hill, P.N., Hsu, D.K., Liu, F.T., 1998, Role of the carboxyl-terminal lectin domain in self-association of galectin-3. Biochemistry 37, 4086- 4092.


116. Schuttling of galectin-3 between lipid raft-indepemdent exocytic and lipid raft-dependent endocytic pathways. International Symposium for PhD Students on Protein Trafficking in Health and Disease, Hamburg, 2010


117. Mo, D., Costa, S.A., Ihrke, G., Youker, R.T., Pastor-Soler, N., Hughey, R.P., Weisz, O.A., 2012, Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells via a galectin-9-dependent mechanism. Mol Biol Cell 23, 3636-3646.


118. Schraml, P., Frew, I.J., Thoma, C.R., Boysen, G., Struckmann, K., Krek, W., Moch, H., 2009, Sporadic clear cell renal cell carcinoma but not the papillary type is characterized by severely reduced frequency of primary cilia. Mod Pathol 22, 31-36.


119. Petruzzelli, L., Takami, M., Humes, H.D., 1999, Structure and function of cell adhesion molecules. Am J Med 106, 467-476.


120. Straube, T., von Mach, T., Greb, C. und Jacob, R. Switch of membrane domains: galectin-3 can do both. Student-organized International Symposium of the DFG Research Training Group 1216, Marburg, 2011


121. Teile dieser Arbeit wurden oder werden in folgenden Artikeln publiziert:


122. Madin, S.H., Andriese, P.C., Darby, N.B., 1957, The in vitro cultivation of tissues of domestic and laboratory animals. Am J Vet Res 18, 932-941.


123. Parczyk, K., Koch-Brandt, C., 1991, The role of carbohydrates in vectorial exocytosis. The secretion of the gp 80 glycoprotein complex in a ricin- resistant mutant of MDCK cells. FEBS Lett 278, 267-270.


124. Ullrich, A., Sures, I., D'Egidio, M., Jallal, B., Powell, T.J., Herbst, R., Dreps, A., Azam, M., Rubinstein, M., Natoli, C., et al., 1994, The secreted tumor- associated antigen 90K is a potent immune stimulator. J Biol Chem 269, 18401-18407.


125. Kammerer, R., Riesenberg, R., Weiler, C., Lohrmann, J., Schleypen, J., Zimmermann, W., 2004, The tumour suppressor gene CEACAM1 is Literaturverzeichnis S e i t e | 202 completely but reversibly downregulated in renal cell carcinoma. J Pathol 204, 258-267.


126. Mostov, K.E., 1994, Transepithelial transport of immunoglobulins. Annu Rev Immunol 12, 63-84.


127. Mitchell, R.A., Bucala, R., 2000, Tumor growth-promoting properties of macrophage migration inhibitory factor (MIF). Semin Cancer Biol 10, 359-366.


128. van Meer, G., Simons, K., 1988, Lipid polarity and sorting in epithelial cells. J Cell Biochem 36, 51-58.


129. Merseburger, A.S., Kramer, M.W., Hennenlotter, J., Simon, P., Knapp, J., Hartmann, J.T., Stenzl, A., Serth, J., Kuczyk, M.A., 2008b, Involvement of decreased Galectin-3 expression in the pathogenesis and progression of prostate cancer. Prostate 68, 72-77.


130. Sarnataro, D., Paladino, S., Campana, V., Grassi, J., Nitsch, L., Zurzolo, C., 2002, PrPC is sorted to the basolateral membrane of epithelial cells independently of its association with rafts. Traffic 3, 810-821.


131. Stechly, L., Morelle, W., Dessein, A.F., Andre, S., Grard, G., Trinel, D., Dejonghe, M.J., Leteurtre, E., Drobecq, H., Trugnan, G., Gabius, H.J., Huet, G., 2009, Galectin-4-regulated delivery of glycoproteins to the brush border membrane of enterocyte-like cells. Traffic 10, 438-450.


132. Straube, T., von Mach, T., Honig, E., Greb, C., Schneider, D., Jacob, R., 2013, PH-dependent recycling of galectin-3 at the apical membrane of epithelial cells. Traffic.


133. van den Brule, F., Califice, S., Castronovo, V., 2004, Expression of galectins in cancer: a critical review. Glycoconj J 19, 537-542.


134. van den Brule, F.A., Buicu, C., Berchuck, A., Bast, R.C., Deprez, M., Liu, F.T., Cooper, D.N., Pieters, C., Sobel, M.E., Castronovo, V., 1996, Expression of the 67-kD laminin receptor, galectin-1, and galectin-3 in advanced human uterine adenocarcinoma. Hum Pathol 27, 1185-1191.


135. van den Brule, F.A., Waltregny, D., Liu, F.T., Castronovo, V., 2000, Alteration of the cytoplasmic/nuclear expression pattern of galectin-3 correlates with prostate carcinoma progression. Int J Cancer 89, 361-367.


136. Poon, S., Rybchyn, M.S., Easterbrook-Smith, S.B., Carver, J.A., Pankhurst, G.J., Wilson, M.R., 2002, Mildly acidic pH activates the extracellular molecular chaperone clusterin. J Biol Chem 277, 39532-39540.


137. Von Mach T., Carlsson MC., Straube T., Nilsson U., Leffler H. und Jacob R. (2013). Ligand-binding and complex formation of galectin-3 is modulated by pH variations. Biochemical Journal


138. Kammerer, R., Popp, T., Hartle, S., Singer, B.B., Zimmermann, W., 2007, Species-specific evolution of immune receptor tyrosine based activation motif-containing CEACAM1-related immune receptors in the dog. BMC Evol Biol 7, 196.


139. Mehul, B., Bawumia, S., Martin, S.R., Hughes, R.C., 1994, Structure of baby hamster kidney carbohydrate-binding protein CBP30, an S-type animal lectin. J Biol Chem 269, 18250-18258.


140. Jung, H., Seong, H.A., Ha, H., 2008, Critical role of cysteine residue 81 of macrophage migration inhibitory factor (MIF) in MIF-induced inhibition of p53 activity. J Biol Chem 283, 20383-20396.


141. Poland, P.A., Rondanino, C., Kinlough, C.L., Heimburg-Molinaro, J., Arthur, C.M., Stowell, S.R., Smith, D.F., Hughey, R.P., 2011, Identification and characterization of endogenous galectins expressed in Madin Darby canine kidney cells. J Biol Chem 286, 6780-6790.


142. Thery, C., Boussac, M., Veron, P., Ricciardi-Castagnoli, P., Raposo, G., Garin, J., Amigorena, S., 2001, Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 166, 7309-7318.


143. Lock, J.G., Stow, J.L., 2005, Rab11 in recycling endosomes regulates the sorting and basolateral transport of E-cadherin. Mol Biol Cell 16, 1744- 1755.


144. Zhao, Q., Barclay, M., Hilkens, J., Guo, X., Barrow, H., Rhodes, J.M., Yu, L.G., 2010, Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis. Mol Cancer 9, 154.


145. Kreitzer, G., Marmorstein, A., Okamoto, P., Vallee, R., Rodriguez-Boulan, E., 2000, Kinesin and dynamin are required for post-Golgi transport of a plasma-membrane protein. Nat Cell Biol 2, 125-127.


146. Rodriguez-Boulan, E., Kreitzer, G., Musch, A., 2005, Organization of vesicular trafficking in epithelia. Nat Rev Mol Cell Biol 6, 233-247.


147. Mellman, I., Nelson, W.J., 2008, Coordinated protein sorting, targeting and distribution in polarized cells. Nat Rev Mol Cell Biol 9, 833-845.


148. Nezil, F.A., Bloom, M., 1992, Combined influence of cholesterol and synthetic amphiphillic peptides upon bilayer thickness in model membranes. Biophys J 61, 1176-1183.


149. Kirshner, J., Chen, C.J., Liu, P., Huang, J., Shively, J.E., 2003, CEACAM1-4S, a cell-cell adhesion molecule, mediates apoptosis and reverts mammary carcinoma cells to a normal morphogenic phenotype in a 3D culture. Proc Natl Acad Sci U S A 100, 521-526.


150. Young, A.N., Amin, M.B., Moreno, C.S., Lim, S.D., Cohen, C., Petros, J.A., Marshall, F.F., Neish, A.S., 2001, Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers. Am J Pathol 158, 1639-1651.


151. Katagiri, A., Watanabe, R., Tomita, Y., 1995, E-cadherin expression in renal cell cancer and its significance in metastasis and survival. Br J Cancer 71, 376-379.


152. Murphy, R.F., Powers, S., Cantor, C.R., 1984, Endosome pH measured in single cells by dual fluorescence flow cytometry: rapid acidification of insulin to pH 6. J Cell Biol 98, 1757-1762.


153. Urban, J., Parczyk, K., Leutz, A., Kayne, M., Kondor-Koch, C., 1987, Constitutive apical secretion of an 80-kD sulfated glycoprotein complex in the polarized epithelial Madin-Darby canine kidney cell line. J Cell Biol 105, 2735-2743.


154. Verkade, P., Harder, T., Lafont, F., Simons, K., 2000, Induction of caveolae in the apical plasma membrane of Madin-Darby canine kidney cells. J Cell Biol 148, 727-739.


155. Vagin, O., Kraut, J.A., Sachs, G., 2009, Role of N-glycosylation in trafficking of apical membrane proteins in epithelia. Am J Physiol Renal Physiol 296, F459-469.


156. Koch, A., Poirier, F., Jacob, R., Delacour, D., 2010, Galectin-3, a novel centrosome-associated protein, required for epithelial morphogenesis. Mol Biol Cell 21, 219-231.


157. Manjithaya, R., Anjard, C., Loomis, W.F., Subramani, S., 2010, Unconventional secretion of Pichia pastoris Acb1 is dependent on GRASP protein, peroxisomal functions, and autophagosome formation. J Cell Biol 188, 537-546.


158. Mishra, R., Grzybek, M., Niki, T., Hirashima, M., Simons, K., 2010, Galectin-9 trafficking regulates apical-basal polarity in Madin-Darby canine kidney epithelial cells. Proc Natl Acad Sci U S A 107, 17633-17638.


159. Salomonsson, E., Carlsson, M.C., Osla, V., Hendus-Altenburger, R., Kahl- Knutson, B., Oberg, C.T., Sundin, A., Nilsson, R., Nordberg-Karlsson, E., Nilsson, U.J., Karlsson, A., Rini, J.M., Leffler, H., 2010, Mutational tuning of galectin-3 specificity and biological function. J Biol Chem 285, 35079- 35091.


160. Moutsatsos, I.K., Wade, M., Schindler, M., Wang, J.L., 1987, Endogenous lectins from cultured cells: nuclear localization of carbohydrate-binding protein 35 in proliferating 3T3 fibroblasts. Proc Natl Acad Sci U S A 84, 6452-6456.


161. Saraboji, K., Hakansson, M., Genheden, S., Diehl, C., Qvist, J., Weininger, U., Nilsson, U.J., Leffler, H., Ryde, U., Akke, M., Logan, D.T., 2012, The carbohydrate-binding site in galectin-3 is preorganized to recognize a sugarlike framework of oxygens: ultra-high-resolution structures and water dynamics. Biochemistry 51, 296-306.


162. Keller, C., Kroening, S., Zuehlke, J., Kunath, F., Krueger, B., Goppelt-Struebe, M., 2012, Distinct mesenchymal alterations in N-cadherin and E-cadherin positive primary renal epithelial cells. PLoS One 7, e43584.


163. Nakahara, S., Raz, A., 2007, Regulation of cancer-related gene expression by galectin-3 and the molecular mechanism of its nuclear import pathway. Cancer Metastasis Rev 26, 605-610.


164. Takenaka, Y., Fukumori, T., Yoshii, T., Oka, N., Inohara, H., Kim, H.R., Bresalier, R.S., Raz, A., 2004, Nuclear export of phosphorylated galectin- 3 regulates its antiapoptotic activity in response to chemotherapeutic drugs. Mol Cell Biol 24, 4395-4406.


165. Robine, S., Huet, C., Moll, R., Sahuquillo-Merino, C., Coudrier, E., Zweibaum, A., Louvard, D., 1985, Can villin be used to identify malignant and undifferentiated normal digestive epithelial cells? Proc Natl Acad Sci U S A 82, 8488-8492.


166. Simons, K., Ikonen, E., 1997, Functional rafts in cell membranes. Nature 387, 569-572.


167. Simons, K., Wandinger-Ness, A., 1990, Polarized sorting in epithelia. Cell 62, 207-210.


168. Kemler, R., 1993, From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet 9, 317-321.


169. Kakehi, K., Oda, Y., Kinoshita, M., 2001, Fluorescence polarization: analysis of carbohydrate-protein interaction. Anal Biochem 297, 111-116.


170. Schneider, D., Greb, C., Koch, A., Straube, T., Elli, A., Delacour, D., Jacob, R., 2010, Trafficking of galectin-3 through endosomal organelles of polarized and non-polarized cells. Eur J Cell Biol 89, 788-798.


171. Jacob, R., Naim, H.Y., 2001, Apical membrane proteins are transported in distinct vesicular carriers. Curr Biol 11, 1444-1450.


172. Jacob, R., Heine, M., Alfalah, M., Naim, H.Y., 2003, Distinct cytoskeletal tracks direct individual vesicle populations to the apical membrane of epithelial cells. Curr Biol 13, 607-612.


173. Thoma, C.R., Frew, I.J., Hoerner, C.R., Montani, M., Moch, H., Krek, W., 2007, pVHL and GSK3beta are components of a primary cilium-maintenance signalling network. Nat Cell Biol 9, 588-595.


174. Kovacikova, J., Winter, C., Loffing-Cueni, D., Loffing, J., Finberg, K.E., Lifton, R.P., Hummler, E., Rossier, B., Wagner, C.A., 2006, The connecting tubule is the main site of the furosemide-induced urinary acidification by the vacuolar H+-ATPase. Kidney Int 70, 1706-1716.


175. Paladino, S., Pocard, T., Catino, M.A., Zurzolo, C., 2006, GPI-anchored proteins are directly targeted to the apical surface in fully polarized MDCK cells. J Cell Biol 172, 1023-1034.


176. Paladino, S., Sarnataro, D., Pillich, R., Tivodar, S., Nitsch, L., Zurzolo, C., 2004, Protein oligomerization modulates raft partitioning and apical sorting of GPI-anchored proteins. J Cell Biol 167, 699-709.


177. Owen, D.M., Rentero, C., Magenau, A., Abu-Siniyeh, A., Gaus, K., 2012, Quantitative imaging of membrane lipid order in cells and organisms. Nat Protoc 7, 24-35.


178. Jacob, R., Alfalah, M., Grunberg, J., Obendorf, M., Naim, H.Y., 2000, Structural determinants required for apical sorting of an intestinal brush-border membrane protein. J Biol Chem 275, 6566-6572.


179. Ladinsky, M.S., Wu, C.C., McIntosh, S., McIntosh, J.R., Howell, K.E., 2002, Structure of the Golgi and distribution of reporter molecules at 20 degrees C reveals the complexity of the exit compartments. Mol Biol Cell 13, 2810-2825.