Mechanisms involved in extracellular matrix-mediated regulation of immune-related genes in mammary epithelial cells

• Main Authors: Hsin-Ju Shen, 沈欣儒
• Other Authors: 李宜儒
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/11979637892253563016

碩士 === 中山醫學大學 === 微生物免疫研究所 === 103 === In mammary glands, epithelial cells contact basement membrane (BM) to form glandular structures with a central lumen. In vitro cultures of mammary cells on Matrigel display this morphology. By contrast, cells cultured on tissue culture plastic form monolayers. Owing to the importance of the microenvironment, we compared gene expression in cells cultured on plastic and Matrigel. Many immune-related genes, including complement component 3 (C3), lipopolysaccharide-binding protein (LBP), CD14, growth arrest-specific 6 (GAS6) and milk fat globule-EGF factor 8 (MFG-E8) were upregulated in cells cultured on BM. We speculate that these genes play a role in lumen formation in mammary acini since cell death and the subsequent clearance of the corpses are essential to establish this tissue architecture. Here we have confirmed our microarray data and found that kinetics of gene expression parallels with that of lumen formation, suggesting that these genes might have a role in luminal clearance of the mammary gland. In addition to substratum type, substratum rigidity, cell shape or their related signaling pathways (Rho/Rac pathways) differentially influence the expression of immune-related genes. Necroptosis positively regulates the expression of these genes since inhibition of cathepsin blocks gene expression and lumen formation. Thus, extracellular matrix might control tissue architecture via modulation of immune-related genes.