CANCER Multiple cross-talk among cancer, stromal and endothelial cells Cancer Cancer cells Matrix(ECM) …… Endothelial cells Pericyte Stromal Endothelial cells cells Stromal cells Interce∥ular Cross talk 2YY制作
ZYY制作 11 CANCER: Multiple Cross-talk among Cancer, stromal and endothelial Cells Cancer cells Stromal cells Endothelial cells Intercellular Cross talk ? Cancer cells Matrix (ECM) Endothelial cells Pericytes Stromal cells
Stroma 1. Fibroblasts in tumor Activated fibroblast GF GFR activated 2. Genetic alteration Juvenile polyposis syndrome (JPS), Cowen syndromeetc Dominant hereditary Stromal cells abnormality, Hamartoma High risk for colon cancer PTEN and others Landscaper Stroma abnormal microenviroment “ Microenviroment of tumor- host interface” 2YY制作 12
ZYY制作 12 Stroma: 1. Fibroblasts in tumor: “Activated fibroblast” GF GF R activated 2. Genetic alteration: Juvenile polyposis syndrome (JPS), Cowen syndrome etc Dominant hereditary Stromal cells abnormality, Hamartoma High risk for colon cancer PTEN and others “Landscaper” “Stroma abnormal microenviroment” “Microenviroment of tumor-host interface
ANGIOGENESIS o Two Processes Endothelial Cells(EC) growth migration Vessel formation Tube formation extension Other cells: Fibroblasts eto 2YY制作 13
ZYY制作 13 ANGIOGENESIS Two Processes Endothelial Cells (EC) growth migration Vessel formation Tube formation extension Other cells: Fibroblasts etc
ANGIOGENESIS/ CANCER INVASION 团 EC Growth control vessel formation Hypoxia Activating hypoxia responses genes( p53) Acidosis VEGF-A Cancer EC) 2YY制作
ZYY制作 14 ANGIOGENESIS / CANCER INVASION EC Growth control & Vessel formation Hypoxia Activating hypoxia responses genes ( p53 ) Acidosis VEGF-A ( Cancer. EC )
Protease/matrix/ Cancer cell invasion/ Angiogenesis Proteases: Degradation of ECM and Cell Associated Proteins MMPs( Marix metallo proteinases), membrane-anchored MMP 2, MMP 9,(Cancer Cell Soluble MMP(fibro, EC Adamalysin -related membrane proteinases BMP 1 metalloproteinases Tissue serine proteinases Inhibitors tPA TIMPs( Tissue inhibitor of MMPs) Thrombin PEX( Degradation product of Plasmin ECM by MMP 2) uPA(EC, fibro. )+uPAR( Cancer 2YY制作 15
ZYY制作 15 Protease / matrix / Cancer cell invasion / Angiogenesis Proteases: Degradation of ECM and Cell Associated Proteins MMPs ( Marix metallo proteinases), membrane - anchored MMP 2, MMP 9, (Cancer Cell) Soluble MMP (fibro, EC) Adamalysin – related membrane proteinases BMP 1 metalloproteinases Tissue serine proteinases tPA UK Thrombin Plasmin uPA ( EC, fibro. ) → uPAR ( Cancer ) Inhibitors PAI TIMPs ( Tissue inhibitor of MMPs) PEX ( Degradation product of ECM by MMP 2 )