Investigation of The Effect of Tumor Extracellular Matrix on Macrophage Matrix Metalloproteinase Expression and Activity

• Main Authors: Shu Chen Huang, 黃淑湞
• Other Authors: H. H. Lin
• Format: Others
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/08715794403336857919

碩士 === 長庚大學 === 生物醫學研究所 === 98 === In tumor microenvironment、the extracellular matrix (ECM) is secreted by tumor cells and its surrounding hematopoietic cells、providing structural scaffolding for cells. These hematopoietic cells、including neutrophil granulocytes、lymphocytes and macrophages are recruited to the tumor site by cytokines、chemokines、and tumor-derived factors. Complex interactions between the different cell types in tumor microenvironment regulate tumor growth、progression、metastasis、and angiogenesis. Tumor-associated macrophages (TAMs) are found in the surroundings of tumor cells and facilitate angiogenesis、ECM breakdown、tissue remodeling、and promote tumor cell motility. Matrix metalloproteinase (MMP)-9 plays a critical role in tumor progression and is common proteinase of TAM. Tissue hypoxia is the common denominator in a variety of pathological conditions、such as malignant tumors. Hypoxia has been shown to induce monocyte and macrophage recruitment、cause their accumulation in hypoxic regions、and alter their morphology、surface molecules expression、viability、phagocytosis and cytokines release. Previous studies have demonstrated that macrophage proteinase expression can be stimulated or inhibited by purified ECM components or their fragments. Recent reports have confirmed that smooth muscle cell (SMC)-ECM stimulates macrophage MMP-9 expression. On the other hand、it has been indicated that hypoxia reduces the output of MMP-9 in monocytes by inhibiting its secretion. Therefore、in the present study、we utilize the tumor-derived ECM and the hypoxic microenvironment to investigate MMP-9 expression and activity by primary monocytes/macrophages. Here we demonstrate that HeLa cell-derived ECM reduces and enhances MMP-9 expression and activity by macrophages and monocytes、respectively. Furthermore、we demonstrate that hypoxia stimulates MMP-9 expression and activity by monocytes、but the effect of hypoxia on MMP-9 expression or activity in macrophages is individual-dependent. We also further discover that tumor ECM affects cell adhesion、morphology and differentiation of macrophages. Consequently、these results suggest that tumor-derived ECM and hypoxia both play important roles in tumor progression influencing MMP-9 expression and activity in monocytes and macrophages、but the levels of influence are individual-dependent.