Role Of Decorin In Epithelial-mesenchymal Transition Of Colon Cancer Cell In Tumor Microenvironment

In the world, colorectal cancer is the third most commonly cancer, and has a high rate of transfer and recurrence. At present, the research of tumor pathogenesis and therapy begin to turn from the tumor cell itself to tumor microenvironment. To suppress occurrence, development, transfer of cancer cells by targeting as tumor microenvironment become a new research hotspot. Decorin is a main component of cell matrix, Some researches suggest that malignancy cancer has been less DCN and lower immunoreactivity than normal colorectal cell through DCN immunohistochemical and ISH, in addition DCN exist in environment can affect generation of cancer cells and growth of vessels.Tumor microenvironment means that the place of tumor growth and which consists of mesenchymal cell and cell matrix. The generation of tumor is depended on cross talk between cancer cell and cell matrix. Cell matrix has been the target to cure cancer because of its important function. EMT is an important mechanism of many epithelial tumor cells which get a malignant phenotype. In microenvironment, EMT happens to cancer cell and promote invasion by interaction between with cell matrix. Studies have found that, during EMT, intercellular adhesion ability is down, cell lose its epithelial character and obtain mesenchyme character, leading to increase the migration and invasion.In this paper, we study that the role of DCN in EMT of colon cancer cell microencironment. As the results:(1) Contruct DCN recombinant proteinContruct DCN recombinant plasmid(pFLAG-ATS-DCN) successfully, and express in E.coli system. Then DCN is separation and purification. Identify its biological activity. All data suggest that DCN can be preparation from prokaryotic expression system, and has function of inhibiting cell proliferation and migration of coloncancer cell.(2) DCN affect morphological change of EMT in microenvironmentBuild indirect co-culture model between LOVO and CCD-18CO successfully, the results show that the ability of invasion from lovo cell in exogenous and endogenous tumor microenviroment during EMT respectively reduce 36.7%,49.4%, and the ability of migration also decrease 45.8%、20%. It means that, overexpression of DCN inhibits the invasion and metastasis of colon cancer cells in tumor microenvironment, and suppress the morphological aspects of EMT process(3) The mechanism of inhibiting EMT by DCN in microenvironmentBuild 3D cell co-culture model between LOVO and CCD-18CO successfully, overexpress DCN from exogenous and endogenous in tumor microenvironment. The expression of MMP2 and MMP9 are decreased, in addition, the expression of E-cadherin are increased, and the expression of mesenchymal markers (vimentin, α-SMA)、EMT markers (Snail, Slug)、cell cycle preotein (CDK4)、inflammatory cellular factor (β-catenin) are reduced. These illustrate that DCN can restrain EMT by inhibiting the proliferation and metastasis of colon cancer cell.In conclusion, DCN play a role in inhibiting the development of EMT in colon cancer cell microenvironment through down-regulation of MMPs、up-regulation of E-cadherin, down-regulation of vimentin, a-SMA, and suppressing invasion and metastasis of LOVO in terms of morphology. Furthermore, DCN can hinder the transformation from epithelial to mesenchyme by reducing the expression of EMT makers (Snai, Slug).