肿瘤分子生物学9. 肿瘤微环境 张志刚.pptVIP

Basement membrane structure Ultrastructure Keratinocyte Basement membrane Keratins BP230 Plectin CD151 Collagen XVII Collagen IV Interstitial collagens Collagen VII LM332 ?6?4 Cell membrane Dermis 30–70 nanometers in thickness BM MMPs BM BM Invasion through the basement membrane Cell proliferation + increasing intra-tumoral pressure = disruption of BM Tumor cell extends filopodia and migrate towards dermal signal Diffusible mediator Dermal alteration The receptor of ECM Integrin family Non-integrin family 18 a subunit, 8 b subunit, more than 20 integrins Syndecan, a-dystroglycan, 67 kD laminin receptor (Laminin receptors) DDRs, GPVI, LAIR-1, uPARAP/Endo180 (collagen receptors) Integrin activation α4 subfamily integrins β4 β7 αE αⅤ β5 β6 β8 β3 αⅡb α10 α1 α2 α5 α8 α9 β1 α4 α7 α3 α6 α11 Collagen-binding integrin Laminin-binding integrins RGD-binding integrins αL β2 αM αX αD Leukocyte integrins ECM receptors- integrin family Roles of Integrins in cancer Regulation of cell survival and apoptosis Roles of Integrins in cancer Regulation of angiogenesis Roles of Integrins in cancer Regulation of migration and invasion Roles of Integrins in cancer Regulation of cancer stem cell Integrins interaction with receptors of growth factor VEGF Receptor (Ruoslahti 2002) TGFB Receptor (Scaffidi et al. 2004) c-MET (HGF receptor) (Sridhar Miranti 2006)) PDGF Receptor (Sridhar Miranti 2006)) EGF Receptor (Bill et al. 2006) Type-1 insulin-like growth factor receptor (Bill et al. 2006) Insulin Receptor (Schneller et al. 1997) Integrin–growth factor and integrin–cytokine receptor crosstalk Integrins in the host defense to cancer Integrins as targets for cancer therapy Roles of MMP in cancer Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases Capable of degrading all kinds of extracellular matrix proteins, but also can process a number of bioactive molecules Involved in the cleavage of cell surface receptors, the release of apoptotic ligands (such as the FAS ligand), a