MATRIX METALLOPROTEASES AND CELL MOTILITY IN MALIGNANT MESOTHELIOMA

摘要: Invasion and metastasis of malignant tumor cells requires destruction migration through extracellular matrix (ECM) such as basement membrane interstitial stroma. The ECM-degrading proteases produced by stromal cell motility play a crucial role in this process. Matrix metalloproreases (MMPs) appear to be particularly important because their capability degrade components ECM. Malignant mesothelioma is an asbestos-associated highly aggressive arising from mesothelial cell-lined surfaces body cavities. It most often present the pleural resulting forms diffuse thickening involved rather than solitary rounded lesions seen other neoplasms. mesotheliomas invade spread underlying or along serosal surfaces. Metastases occur up 75 % patients. There no effective standard treatment for mesothelioma. general aim thesis understand why surrounding tissues metastasize. Using human lines model, goal was to: (i) investigate expression production MMPs cells. All investigated expressed mRNA MMP-1, MMP-2, MMP-3, MMP-9 6/8 MMP-7, 3/8 MMP-10. MMP-11 not detected any tested. MMP -2 -9 degraded gelatin, whereas MMP-3 laminin, fibronectin vitronectin; (ii) exposure different growth factors, including epidermal factor (EGF), transforming factor-α (TGF-α), amphiregulin (AR), heparin-binding EGF-like (HB-EGF), β-cellulin (BTC), stem (SCF), insulin-like (IGF)-I, -II, acidic-fibroblast (aFGF), basic-FGF (bFGF) hepatocyte (HGF), increased and/or MMP-3. Production MMP-2 affected factors used study; (iii) examine (chemotaxis chemokinesis) induced multiple EGF, TGF-α, AR, HB-EGF, BTC, IGF-I, IGF-II SCF stimulated chemotactic chemokinetic tested, none aFGF, bFGF, granulocyte-macrophage colony-stimulating (GM-CSF) interleukin-6 (IL-6) same cells; (iv) study novel EGF receptor-tyrosine kinase (EGFR-TK) inhibitors (ZD1839, OSI-774, CI-1033) on proliferation invasive behaviour vitro. three drugs inhibited TGF-α cellular proliferation, (chemotaxis) In conclusion, we have described expression, regulation addition, our results indicate that may invasion. Furthermore, contribute We also demonstrated EGFR-TK inhibit suggesting these become strategy LIST OF PUBLICATIONS This based following articles, which are referred text with roman numbers (I-IV). I. Zhiwen Liu, Anna Ivanoff Julius Klominek. (2001) Expression activity metalloproteases lines. Int. J. Cancer. 91,638-643 II. Liu (2003) Regulation factors. Thorax. 58,198203 III. (2004) Chemotaxis chemokinesis Anticancer Research. 24 (3a), 1625-30 IV. Inhibition tyrosine inhibitors. Neoplasia. 6 (6), press