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Osteopontin splice variants expressed by breast tumors regulate monocyte activation via MCP-1 and TGF-β1

Cellular & Molecular Immunology 2013年第2期10卷 176-182页

作者： Jintang Sun Alei Feng Songyu Chen Yun Zhang Qi Xie Meixiang Yang Qianqian Shao Jia Liu Qifeng Yang Beihua Kong Xun Qu Institute of Basic Medical Sciences Jinan China Department of Obstetrics and Gynecology Jinan China Key Laboratory of Cardiovascular Proteomics of Shandong Province Qilu Hospital Shandong University Jinan China

Osteopontin （opn）, a multifunctional glycoprotein, has three transcripts that have distinct roles in tumors in vitro. Whether opn transcripts have different functions in tumor processes in vivo is unclear. It has been reported that immune cell-derived opn can promote tumor formation. We propose a hypothesis that tumor-derived opn may facilitate tumor immune escape by affecting immune cell differentiation and function. In this study, we constructed lentiviral expression vectors of opn transcripts and transfected them into the MCF-7 cell line. MCF-7 cells transfected with opn transcripts were injected into the armpit of nude mice, and tumor growth was monitored. The results showed that all opn transcripts promoted local tumor formation, but that there was no significant difference among transcripts. We also investigated the effect of the opn expressed by tumor cells on monocyte differentiation by coculturing monocytes with tumor supernatant. We found opn-c upregulated CD163 levels compared with opn-a and opn-b; however, none of the transcripts affected HLA-DR and CD206 levels. All opn transcripts significantly inhibited TNF-α and enhanced IL-10 production by monocytes. Furthermore, we found that the overexpression of opn transcripts significantly upregulated TGF-β1 and MCP-1 production by tumor cells. Using neutralizing antibody and recombinant cytokines, we found that opn overexpressed by tumor cells regulates the production of TNF-α and IL-10 by monocytes partly via MCP-1 and TGF-β1, respectively. Collectively, our results show that opn transcripts have no distinct role in breast cancer formation in vivo. We also demonstrate that opn regulates the alternative activation of monocytes via TGF-β1 and MCP-1, which may represent an additional mechanism for tumor immune escape.

关键词： alternative activation of monocytes immune escape opn transcripts MCP-1 TGF-I31

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