Expression der Matrix-Metalloproteinasen MMP-2, -7, -9 und -13 und ihrer Inhibitoren TIMP-1, -2 und -3 in Plattenepithelkarzinomen des oberen Aerodigestivtraktes

Plattenepithelkarzinome des oberen Aerodigestivtraktes stehen in Europa an sechster Stelle in der Häufigkeit ihres Auftretens und weisen in fortgeschrittenen Stadien trotz moderner Behandlungsmethoden eine relativ geringe 5-Jahres-Überlebensrate auf. Diese ist vor allem auf die hohe, in der Regel ly...

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Bibliographische Detailangaben
1. Verfasser: Falkenberg, Sonja
Beteiligte: Werner, Jochen A. (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Veröffentlicht: Philipps-Universität Marburg 2004
Hals- Nasen- und Ohrenheilkunde
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Inhaltsangabe: The occurrence of squamous cell carcinomas of the head and neck is relatively lower than that of the more common carcinomas of lung, breast or bowel. Its 5-years-survival-rate is poorly despite modern therapies. The main reason for that is the high risk of lymphatic metastasis in early stages of the disease. Therefore, research is aimed towards the development of molecular markers which would allow to estimate the individual risk of metastasis and tumor aggressiveness pre-operatively. Matrix-metalloproteinases are of special interest in this context. Matrix-metalloproteinases are a family of endopeptidases containing ionic Zinc at their site of activity. In addition to other biological functions, all members of the family are able to degrade extracellular matrix. MMPs are regulated at several stages of their synthesis by various factors, amongst them specific inhibitors, TIMPs. MMPs and their inhibitors play a vital role in various physiological and pathological processes, e.g. wound healing and the spread and metastasis of malignant tumors. MMP-2 and -9, unlike other MMPs, are able to degrade Type-IV collagene, a collagene needed to build basement membranes. With this in mind, RNA-expression of MMP-2, -7, -9 and -13 and of TIMP-1, -2 and -3 in HNSCC-tissues and cell-lines was examined. RNA was extracted, RT-PCR and electrophoresis were performed. Results were interpreted semiquantitatively evaluated with statistic measures. RNA of MMPs and TIMPs was detectable in tissues as well as cell-lines. MMP-13 RNA could be detected most samples, MMP-2 RNA was the rarest one. Statistically significant correlations existed between MMP-13 RNA-levels and possible lymphnode metastasis and MMP-9 RNA-levels and metastatic spread. Further results indicated a possible connection between MMP-2 and -9 RNA-levels and a progressing tumor disease. RNA-expression in cell-lines was similar to that in tissue samples, but on a generally lower level. There were neither correlations between MMP-RNA-signals and the localisation of a HNSCC, nor congruent patterns of expression. Summarizing the results it can be said that the MMPs and TIMPs examined play a role in HNSCC progression and metastasis. A final judgement of their possible prognostic value is not yet possible at present.