CANCER: Multiple Cross-talk among Cancer,stromal and endothelial Cells Cancer cells Cancer cells Matrix (ECM) Endothelial cells /尘 Pericytes Stromal Endothelial cells cells Stromal cells Intercellular Cross talk ZY制作 11
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 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” ZYY制作
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 Two Processes Endothelial Cells (EC) growth migration Vessel formation Tube formation extension Other cells:Fibroblasts etc ZY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 EC Growth control Vessel formation Hypoxia Activating hypoxia responses genes(p53 Acidosis VEGF-A (Cancer.EC) ZYY制作 14
ZYY制作 14 ANGIOGENESIS / CANCER INVASION EC Growth control & Vessel formation Hypoxia Activating hypoxia responses genes ( p53 ) Acidosis VEGF-A ( Cancer. EC )
2 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 PAI UK TIMPs Tissue inhibitor of MMPs) Thrombin PEX Degradation product of Plasmin ECM by MMP 2) uPA(EC,fibro.）-→uPAR(Cancer） ZY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 )