Integrinexpression und integrinvermittelte VEGF-Produktion maligner Schilddrüsenzellen in vitro

Schilddrüsenkarzinome sind die häufigste maligne Erkrankung endokriner Organe. Als entscheidender Faktor für die Tumorprogression wurde die Fähigkeit der Schilddrüsenkarzinomzellen zur Angiogenese erkannt, die ihnen ein uneingeschränktes Wachstum und die Invasion des umgebenden Gewebes ermöglicht....

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1. Verfasser: Amari, Tarik
Beteiligte: Zielke, Andreas (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Deutsch
Veröffentlicht: Philipps-Universität Marburg 2009
Operative Medizin
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topic Extrazelluläre Matrix
Integrins
Thyroid carcinomas
Extracellular matrix
Vascular endothelial Growth Factor
Integrine
Medizin, Gesundheit
Angiogenesis
Angiogenese
VEGF
Schilddrüsenkrebs
spellingShingle Extrazelluläre Matrix
Integrins
Thyroid carcinomas
Extracellular matrix
Vascular endothelial Growth Factor
Integrine
Medizin, Gesundheit
Angiogenesis
Angiogenese
VEGF
Schilddrüsenkrebs
Integrinexpression und integrinvermittelte VEGF-Produktion maligner Schilddrüsenzellen in vitro
Amari, Tarik
Thyroid carcinomas are the most frequent malignancy of endocrine organs. They can be classified in four entities of various differentiation and prognosis. Follicular, papillary, anaplastic and medullary carcinomas. An important factor of cancer progression was recognized in the capacity of thyroid carcinoma cells to angiogenesis, procuring them an unlimited growth and the invasion of the surrounding tissue. For a great number of carcinomas the angiogenesis is a capital pathophysiological step. For this reason the antiangiogen therapy places itself more and more in the center of scientific interest. The aim of this thesis was to give a survey of the interaction of integrins, VEGF and the extracellular matrix (ECM) by using a cell culture model of different thyroid carcinomas. A better understanding of the interaction of these factors essential to the angiogenesis is the precondition for the development of effective therapy strategies. In the test series the Hurthle cell line XTC, the follicular cell line HTC+, the anaplastic cell line and the cell line Hth74 as well as a cell line isolated from natural thyroid tissue (Thy1) were examined. The spectrum of the integrins of the oncogenic (XTC, HTC+, Hth74) and the normal cells (Thy1) was found out by immunhistochemical tests. All cells expressed a great spectrum of integrins whereas in comparison the cell line of normal tissue contains the smallest spectrum. Histiotypical associated similarities appear among the cancer cell lines, out of which the undifferentiated (Hth74) shows the largest spectrum. These results suggest that the thyroid cancer cells dispose of an enlarged possibility of adhesion to ECM. It is assured that the spectrum and the extent of the integrin expression of cancer cells correlate with their abilities of proliferation and invasion. This change of their integrin expression has radical effects on their biological properties. In this context the linking to Fibronectin seems to play an important role. Two cancer cell lines (XTC, HTC+) were incubated on different matrix components and the VEGF expression was examined via ELISA. Fibronectin (FN) was the only of the tested matrix proteins that induced an increase of VEGF secretion. The stimulation of the VEGF secretion by FN confirms the important role of FN in angiogenesis which is also described in the literature. The incubation of the two cancer cell lines (XTC, HTC+) without matrix components with a choice of the best examined and available integrin antibodies at this time had no effect on the VEGF secretion. Since the blockade of integrins had no reducing effect on the high VEGF basic output of thyroid cancer cells, the regulation of the VEGF secretion is assumed to be very complex and does not only depend on integrin signalling. In a further examination of XTC cells, integrin antibodies and integrin blocking RGD sequences (RGDS) were used to suppress the stimulating effect of FN on VEGF. The RGD sequences increased the intra- and extra cellular VEGF concentration of the XTC cells proportional to the RGDS-concentration. The FN specific integrin antibodies had no influence on the VEGF secretion. Since the RGDS led to an increase of the VEGF concentration and not to a suppression, as expected, it must be discussed, that they dispose of an intrinsic activity with initiation of intracellular signal pathways in the sense of an “Outside-in” signalling. The VEGF-synthesis of thyroid cancers seems thus to be influenced by the extra cellular matrix (FN) via integrins. The influence of VEGF on the integrin spectrum of XTC cells was analysed by FACS. There was shown no change of the integrin expression by VEGF. The importance of growth factors on the integrin expression is demonstrated in the literature. The examination of the influence of VEGF on the integrin expression of the XTC cells in the sense of an “Inside-out“ control loop could not prove an autocrine control loop in spite of the well known close interaction of integrins and VEGF receptors. It could be shown that thyroid cancers similar to other cancers depend on the expression of integrins and their interaction with the extra cellular matrix (ECM) in order to use angiogenesis. This thesis represents a detailed examination of a great number of integrins and is one of the first which has tried to exert influence on the VEGF secretion of thyroid cancer cells via RGDS and integrin antibodies. Further examinations are needed to explore these detailed interactions. Inhibitors of the integrin mediated angiogenesis like Volociximab® will be a focus of the medical cancer therapy in the future. Today they are already a useful option of therapy besides the chemotherapy.
author2 Zielke, Andreas (Prof. Dr.)
author2_role ths
institution Operative Medizin
first_indexed 2010-03-16T00:00:00Z
title Integrinexpression und integrinvermittelte VEGF-Produktion maligner Schilddrüsenzellen in vitro
title_short Integrinexpression und integrinvermittelte VEGF-Produktion maligner Schilddrüsenzellen in vitro
title_full Integrinexpression und integrinvermittelte VEGF-Produktion maligner Schilddrüsenzellen in vitro
title_fullStr Integrinexpression und integrinvermittelte VEGF-Produktion maligner Schilddrüsenzellen in vitro
title_full_unstemmed Integrinexpression und integrinvermittelte VEGF-Produktion maligner Schilddrüsenzellen in vitro
title_sort Integrinexpression und integrinvermittelte VEGF-Produktion maligner Schilddrüsenzellen in vitro
description Schilddrüsenkarzinome sind die häufigste maligne Erkrankung endokriner Organe. Als entscheidender Faktor für die Tumorprogression wurde die Fähigkeit der Schilddrüsenkarzinomzellen zur Angiogenese erkannt, die ihnen ein uneingeschränktes Wachstum und die Invasion des umgebenden Gewebes ermöglicht. Die Angiogenese ist für eine Vielzahl von Karzinomen ein pathophysiologisch entscheidender Schritt. Aus diesem Grund rückt die antiangiogene Therapie immer mehr in den Mittelpunkt des wissenschaftlichen Interesses. Das Ziel dieser Arbeit war es, anhand eines Zellkulturmodells verschiedener Schilddrüsenkarzinome ein Bild der Interaktion von Integrinen, VEGF und der extrazellulären Matrix (ECM) zu erstellen. Das bessere Verständnis des Zusammenwirkens dieser für die Angiogenese essentiellen Faktoren ist die Voraussetzung für die Entwicklung effektiver Therapiestrategien. In den Versuchsreihen wurden die Hürtelzelllinie XTC, die follikuläre Zelllinie HTC+, die anaplastische Zelllinie Hth74 sowie eine aus normalem Schilddrüsengewebe isolierte Zelllinie Thy1 untersucht. Immunhistochemisch wurde das Integrinspektrum der onkogenen (XTC, HTC+, Hth74) und normalen Schilddrüsenzellen (Thy1) ermittelt. Alle Zellen exprimieren eine große Bandbreite von Integrinen, wobei die Zelllinie des Normalgewebes im Vergleich das schmalste Spektrum besitzt. Es zeigen sich histiotyp-assoziierte Ähnlichkeiten unter den Tumorzelllinien, von denen die entdifferenzierteste (Hth74) das breiteste Spektrum aufweist. Diese Ergebnisse legen nahe, dass die Schilddrüsenkarzinomzellen über ein erweitertes Bindungsvermögen zur ECM verfügen. Man geht davon aus, dass das Spektrum und das Ausmaß der Integrinexpression onkogener Zellen mit ihren Fähigkeiten zu Proliferation und Invasion korrelieren. Diese Veränderung des Integrinspektrums hat tiefgreifende Auswirkungen auf ihre Eigenschaften, hierbei scheint besonders die Bindung an Fibronektin eine wichtige Rolle zu spielen. Zwei Tumorzelllinien (XTC, HTC+) wurden auf verschiedenen Matrixkomponenten inkubiert und mittels ELISA auf ihre VEGF-Sekretion untersucht. Fibronektin (FN) führte als einziges der getesteten Matrixproteine zu einer erhöhten VEGF-Sekretion. Die steigernde Wirkung von FN auf die VEGF-Sekretion untermauert die in der Literatur beschriebene wichtige Rolle von FN in der Angiogenese. Die Inkubation der Tumorzelllinien (XTC, HTC+) ohne Matrixkomponenten mit einer Auswahl der zu dieser Zeit (2000 bis 2002) am besten untersuchten und verfügbaren Integrinantikörper hatte keinen Einfluss auf ihre VEGF-Sekretion. Da die Blockierung der Integrine keine Reduktion der hohen VEGF-Basissekretion der Schilddrüsenkarzinomzellen bewirkte, ist vom Vorliegen einer komplexen Steuerung der VEGF-Sekretion auszugehen, die nicht ausschließlich von integrinvermittelten Signalen abhängt. In einer weiteren Untersuchung an XTC-Zellen wurden integrinblockierende RGD-Sequenzen bzw. Antikörper eingesetzt, um den stimulierenden Effekt von FN auf VEGF aufzuheben. Die RGD-Sequenzen steigerten die extra- und intrazelluläre VEGF-Konzentration der XTC-Zellen in einem klaren Dosis-Wirkungseffekt. Die FN-spezifischen Integrinantikörper hatten keinen Einfluss auf die VEGF-Sekretion. Da die RGD-Sequenzen, anstelle der erwarteten Absenkung, zu einer Steigerung der VEGF-Konzentration führten, muss diskutiert werden, dass sie über eine intrinsische Aktivität mit Initiierung intrazellulärer Signalwege im Sinne einer Outside-in Signaltransduktion verfügen. Die VEGF-Synthese der Schilddrüsentumoren scheint somit integrinvermittelt von der extrazellulären Matrix (FN) beeinflusst zu sein. Der Einfluss von VEGF auf das Integrinspektrum von XTC-Zellen wurde mittels FACS analysiert. Es zeigte sich keine Veränderung der Integrinkonfiguration durch VEGF. Die Bedeutung von Wachstumsfaktoren für die Integrinexpression ist nachgewiesen. Die Untersuchung des Einflusses von VEGF auf die Integrinexpression der XTC-Zellen im Sinne eines Inside-out Regelkreises konnte trotz der bekannten engen Interaktion von VEGF-Rezeptoren und Integrinen keinen autokrinen Regelkreis nachweisen. Es konnte gezeigt werden, dass Schilddrüsenkarzinome ähnlich wie andere Karzinome auf die Expression von Integrinen und deren Interaktion mit der extrazellulären Matrix angewiesen sind, um sich der Angiogenese bedienen zu können. Diese Arbeit stellt eine ausführliche Untersuchung einer Vielzahl von Integrinen dar und ist eine der Ersten, die versucht, über RGD-Sequenzen und blockierende Antikörper Einfluss auf die VEGF-Sekretion von Schilddrüsenkarzinomzellen zu nehmen. Inhibitoren der integrinvermittelten Angiogenese werden in der Zukunft einen Schwerpunkt der medikamentösen Tumorbehandlung bilden, schon heute stellen sie neben der Chemotherapie eine wertvolle Therapieoption dar.
publishDate 2009
era_facet 2009
url http://archiv.ub.uni-marburg.de/diss/z2010/0046/pdf/dta.pdf
author Amari, Tarik
language German
building Medizin
contents Thyroid carcinomas are the most frequent malignancy of endocrine organs. They can be classified in four entities of various differentiation and prognosis. Follicular, papillary, anaplastic and medullary carcinomas. An important factor of cancer progression was recognized in the capacity of thyroid carcinoma cells to angiogenesis, procuring them an unlimited growth and the invasion of the surrounding tissue. For a great number of carcinomas the angiogenesis is a capital pathophysiological step. For this reason the antiangiogen therapy places itself more and more in the center of scientific interest. The aim of this thesis was to give a survey of the interaction of integrins, VEGF and the extracellular matrix (ECM) by using a cell culture model of different thyroid carcinomas. A better understanding of the interaction of these factors essential to the angiogenesis is the precondition for the development of effective therapy strategies. In the test series the Hurthle cell line XTC, the follicular cell line HTC+, the anaplastic cell line and the cell line Hth74 as well as a cell line isolated from natural thyroid tissue (Thy1) were examined. The spectrum of the integrins of the oncogenic (XTC, HTC+, Hth74) and the normal cells (Thy1) was found out by immunhistochemical tests. All cells expressed a great spectrum of integrins whereas in comparison the cell line of normal tissue contains the smallest spectrum. Histiotypical associated similarities appear among the cancer cell lines, out of which the undifferentiated (Hth74) shows the largest spectrum. These results suggest that the thyroid cancer cells dispose of an enlarged possibility of adhesion to ECM. It is assured that the spectrum and the extent of the integrin expression of cancer cells correlate with their abilities of proliferation and invasion. This change of their integrin expression has radical effects on their biological properties. In this context the linking to Fibronectin seems to play an important role. Two cancer cell lines (XTC, HTC+) were incubated on different matrix components and the VEGF expression was examined via ELISA. Fibronectin (FN) was the only of the tested matrix proteins that induced an increase of VEGF secretion. The stimulation of the VEGF secretion by FN confirms the important role of FN in angiogenesis which is also described in the literature. The incubation of the two cancer cell lines (XTC, HTC+) without matrix components with a choice of the best examined and available integrin antibodies at this time had no effect on the VEGF secretion. Since the blockade of integrins had no reducing effect on the high VEGF basic output of thyroid cancer cells, the regulation of the VEGF secretion is assumed to be very complex and does not only depend on integrin signalling. In a further examination of XTC cells, integrin antibodies and integrin blocking RGD sequences (RGDS) were used to suppress the stimulating effect of FN on VEGF. The RGD sequences increased the intra- and extra cellular VEGF concentration of the XTC cells proportional to the RGDS-concentration. The FN specific integrin antibodies had no influence on the VEGF secretion. Since the RGDS led to an increase of the VEGF concentration and not to a suppression, as expected, it must be discussed, that they dispose of an intrinsic activity with initiation of intracellular signal pathways in the sense of an “Outside-in” signalling. The VEGF-synthesis of thyroid cancers seems thus to be influenced by the extra cellular matrix (FN) via integrins. The influence of VEGF on the integrin spectrum of XTC cells was analysed by FACS. There was shown no change of the integrin expression by VEGF. The importance of growth factors on the integrin expression is demonstrated in the literature. The examination of the influence of VEGF on the integrin expression of the XTC cells in the sense of an “Inside-out“ control loop could not prove an autocrine control loop in spite of the well known close interaction of integrins and VEGF receptors. It could be shown that thyroid cancers similar to other cancers depend on the expression of integrins and their interaction with the extra cellular matrix (ECM) in order to use angiogenesis. This thesis represents a detailed examination of a great number of integrins and is one of the first which has tried to exert influence on the VEGF secretion of thyroid cancer cells via RGDS and integrin antibodies. Further examinations are needed to explore these detailed interactions. Inhibitors of the integrin mediated angiogenesis like Volociximab® will be a focus of the medical cancer therapy in the future. Today they are already a useful option of therapy besides the chemotherapy.
publisher Philipps-Universität Marburg
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genre Medical sciences, Medicine
genre_facet Medical sciences, Medicine
topic_facet Medizin, Gesundheit
title_alt Integrinexpression and integrin-mediated VEGF-production of malignant thyroid cancer cells in vitro
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Variants of the cell recognition site of fibronectin that retain attachment-promoting activity Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis. Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis 2010-03-16 Integrinexpression und integrinvermittelte VEGF-Produktion maligner Schilddrüsenzellen in vitro Schilddrüsenkarzinome sind die häufigste maligne Erkrankung endokriner Organe. Als entscheidender Faktor für die Tumorprogression wurde die Fähigkeit der Schilddrüsenkarzinomzellen zur Angiogenese erkannt, die ihnen ein uneingeschränktes Wachstum und die Invasion des umgebenden Gewebes ermöglicht. Die Angiogenese ist für eine Vielzahl von Karzinomen ein pathophysiologisch entscheidender Schritt. Aus diesem Grund rückt die antiangiogene Therapie immer mehr in den Mittelpunkt des wissenschaftlichen Interesses. Das Ziel dieser Arbeit war es, anhand eines Zellkulturmodells verschiedener Schilddrüsenkarzinome ein Bild der Interaktion von Integrinen, VEGF und der extrazellulären Matrix (ECM) zu erstellen. Das bessere Verständnis des Zusammenwirkens dieser für die Angiogenese essentiellen Faktoren ist die Voraussetzung für die Entwicklung effektiver Therapiestrategien. In den Versuchsreihen wurden die Hürtelzelllinie XTC, die follikuläre Zelllinie HTC+, die anaplastische Zelllinie Hth74 sowie eine aus normalem Schilddrüsengewebe isolierte Zelllinie Thy1 untersucht. Immunhistochemisch wurde das Integrinspektrum der onkogenen (XTC, HTC+, Hth74) und normalen Schilddrüsenzellen (Thy1) ermittelt. Alle Zellen exprimieren eine große Bandbreite von Integrinen, wobei die Zelllinie des Normalgewebes im Vergleich das schmalste Spektrum besitzt. Es zeigen sich histiotyp-assoziierte Ähnlichkeiten unter den Tumorzelllinien, von denen die entdifferenzierteste (Hth74) das breiteste Spektrum aufweist. Diese Ergebnisse legen nahe, dass die Schilddrüsenkarzinomzellen über ein erweitertes Bindungsvermögen zur ECM verfügen. Man geht davon aus, dass das Spektrum und das Ausmaß der Integrinexpression onkogener Zellen mit ihren Fähigkeiten zu Proliferation und Invasion korrelieren. Diese Veränderung des Integrinspektrums hat tiefgreifende Auswirkungen auf ihre Eigenschaften, hierbei scheint besonders die Bindung an Fibronektin eine wichtige Rolle zu spielen. Zwei Tumorzelllinien (XTC, HTC+) wurden auf verschiedenen Matrixkomponenten inkubiert und mittels ELISA auf ihre VEGF-Sekretion untersucht. Fibronektin (FN) führte als einziges der getesteten Matrixproteine zu einer erhöhten VEGF-Sekretion. Die steigernde Wirkung von FN auf die VEGF-Sekretion untermauert die in der Literatur beschriebene wichtige Rolle von FN in der Angiogenese. Die Inkubation der Tumorzelllinien (XTC, HTC+) ohne Matrixkomponenten mit einer Auswahl der zu dieser Zeit (2000 bis 2002) am besten untersuchten und verfügbaren Integrinantikörper hatte keinen Einfluss auf ihre VEGF-Sekretion. Da die Blockierung der Integrine keine Reduktion der hohen VEGF-Basissekretion der Schilddrüsenkarzinomzellen bewirkte, ist vom Vorliegen einer komplexen Steuerung der VEGF-Sekretion auszugehen, die nicht ausschließlich von integrinvermittelten Signalen abhängt. In einer weiteren Untersuchung an XTC-Zellen wurden integrinblockierende RGD-Sequenzen bzw. Antikörper eingesetzt, um den stimulierenden Effekt von FN auf VEGF aufzuheben. Die RGD-Sequenzen steigerten die extra- und intrazelluläre VEGF-Konzentration der XTC-Zellen in einem klaren Dosis-Wirkungseffekt. Die FN-spezifischen Integrinantikörper hatten keinen Einfluss auf die VEGF-Sekretion. Da die RGD-Sequenzen, anstelle der erwarteten Absenkung, zu einer Steigerung der VEGF-Konzentration führten, muss diskutiert werden, dass sie über eine intrinsische Aktivität mit Initiierung intrazellulärer Signalwege im Sinne einer Outside-in Signaltransduktion verfügen. Die VEGF-Synthese der Schilddrüsentumoren scheint somit integrinvermittelt von der extrazellulären Matrix (FN) beeinflusst zu sein. Der Einfluss von VEGF auf das Integrinspektrum von XTC-Zellen wurde mittels FACS analysiert. Es zeigte sich keine Veränderung der Integrinkonfiguration durch VEGF. Die Bedeutung von Wachstumsfaktoren für die Integrinexpression ist nachgewiesen. Die Untersuchung des Einflusses von VEGF auf die Integrinexpression der XTC-Zellen im Sinne eines Inside-out Regelkreises konnte trotz der bekannten engen Interaktion von VEGF-Rezeptoren und Integrinen keinen autokrinen Regelkreis nachweisen. Es konnte gezeigt werden, dass Schilddrüsenkarzinome ähnlich wie andere Karzinome auf die Expression von Integrinen und deren Interaktion mit der extrazellulären Matrix angewiesen sind, um sich der Angiogenese bedienen zu können. Diese Arbeit stellt eine ausführliche Untersuchung einer Vielzahl von Integrinen dar und ist eine der Ersten, die versucht, über RGD-Sequenzen und blockierende Antikörper Einfluss auf die VEGF-Sekretion von Schilddrüsenkarzinomzellen zu nehmen. Inhibitoren der integrinvermittelten Angiogenese werden in der Zukunft einen Schwerpunkt der medikamentösen Tumorbehandlung bilden, schon heute stellen sie neben der Chemotherapie eine wertvolle Therapieoption dar. 2009 Thyroid carcinomas are the most frequent malignancy of endocrine organs. They can be classified in four entities of various differentiation and prognosis. Follicular, papillary, anaplastic and medullary carcinomas. An important factor of cancer progression was recognized in the capacity of thyroid carcinoma cells to angiogenesis, procuring them an unlimited growth and the invasion of the surrounding tissue. For a great number of carcinomas the angiogenesis is a capital pathophysiological step. For this reason the antiangiogen therapy places itself more and more in the center of scientific interest. The aim of this thesis was to give a survey of the interaction of integrins, VEGF and the extracellular matrix (ECM) by using a cell culture model of different thyroid carcinomas. A better understanding of the interaction of these factors essential to the angiogenesis is the precondition for the development of effective therapy strategies. In the test series the Hurthle cell line XTC, the follicular cell line HTC+, the anaplastic cell line and the cell line Hth74 as well as a cell line isolated from natural thyroid tissue (Thy1) were examined. The spectrum of the integrins of the oncogenic (XTC, HTC+, Hth74) and the normal cells (Thy1) was found out by immunhistochemical tests. All cells expressed a great spectrum of integrins whereas in comparison the cell line of normal tissue contains the smallest spectrum. Histiotypical associated similarities appear among the cancer cell lines, out of which the undifferentiated (Hth74) shows the largest spectrum. These results suggest that the thyroid cancer cells dispose of an enlarged possibility of adhesion to ECM. It is assured that the spectrum and the extent of the integrin expression of cancer cells correlate with their abilities of proliferation and invasion. This change of their integrin expression has radical effects on their biological properties. In this context the linking to Fibronectin seems to play an important role. Two cancer cell lines (XTC, HTC+) were incubated on different matrix components and the VEGF expression was examined via ELISA. Fibronectin (FN) was the only of the tested matrix proteins that induced an increase of VEGF secretion. The stimulation of the VEGF secretion by FN confirms the important role of FN in angiogenesis which is also described in the literature. The incubation of the two cancer cell lines (XTC, HTC+) without matrix components with a choice of the best examined and available integrin antibodies at this time had no effect on the VEGF secretion. Since the blockade of integrins had no reducing effect on the high VEGF basic output of thyroid cancer cells, the regulation of the VEGF secretion is assumed to be very complex and does not only depend on integrin signalling. In a further examination of XTC cells, integrin antibodies and integrin blocking RGD sequences (RGDS) were used to suppress the stimulating effect of FN on VEGF. The RGD sequences increased the intra- and extra cellular VEGF concentration of the XTC cells proportional to the RGDS-concentration. The FN specific integrin antibodies had no influence on the VEGF secretion. Since the RGDS led to an increase of the VEGF concentration and not to a suppression, as expected, it must be discussed, that they dispose of an intrinsic activity with initiation of intracellular signal pathways in the sense of an “Outside-in” signalling. The VEGF-synthesis of thyroid cancers seems thus to be influenced by the extra cellular matrix (FN) via integrins. The influence of VEGF on the integrin spectrum of XTC cells was analysed by FACS. There was shown no change of the integrin expression by VEGF. The importance of growth factors on the integrin expression is demonstrated in the literature. The examination of the influence of VEGF on the integrin expression of the XTC cells in the sense of an “Inside-out“ control loop could not prove an autocrine control loop in spite of the well known close interaction of integrins and VEGF receptors. It could be shown that thyroid cancers similar to other cancers depend on the expression of integrins and their interaction with the extra cellular matrix (ECM) in order to use angiogenesis. This thesis represents a detailed examination of a great number of integrins and is one of the first which has tried to exert influence on the VEGF secretion of thyroid cancer cells via RGDS and integrin antibodies. Further examinations are needed to explore these detailed interactions. Inhibitors of the integrin mediated angiogenesis like Volociximab® will be a focus of the medical cancer therapy in the future. Today they are already a useful option of therapy besides the chemotherapy. urn:nbn:de:hebis:04-z2010-00460 Integrinexpression and integrin-mediated VEGF-production of malignant thyroid cancer cells in vitro 2011-08-10 opus:2598 ths Prof. Dr. Zielke Andreas Zielke, Andreas (Prof. Dr.) Amari, Tarik Amari Tarik Philipps-Universität Marburg
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