Tumacrophage: macrophages transformed into tumor stem-like cells by virulent genetic material from tumor cells
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Yizhuang Zhang1,*, Na Zhou1,*, Xiuyan Yu1,*, Xuehui Zhang1, Shanxin Li1, Zhen Lei5, Ruobi Hu1, Hui Li1, Yiqing Mao1, Xi Wang1, Jinshu Zhang2, Yuan Li3, Hongyan Guo3, David M. Irwin4, Gang Niu5 and Huanran Tan1
1Department of Pharmacology, Peking University, Beijing, China
2Department of Clinical Laboratory, The 305 Hospital of People’s Liberation Army, Beijing, China
3Department of Gynaecology and Obstetrics, Peking University Third Hospital, Beijing, China
4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
5N & N Genetech Company, Ltd., Beijing, China
*These authors have contributed equally to this work
Huanran Tan, email: [email protected]
Gang Niu, email: [email protected]
David M. Irwin, email: [email protected]
Keywords: macrophages, circulating tumor cells, apoptosis, phagocytosis, epithelial tumors
Received: May 04, 2017 Accepted: June 20, 2017 Published: July 18, 2017
Tumor-associated macrophages are regarded as tumor-enhancers as they have key roles in the subversion of adaptive immunity and in inflammatory circuits that promote tumor progression. Here, we show that cancer cells can subvert macrophages yielding cells that have gained pro-tumor functions. When macrophages isolated from mice or humans are co-cultured with dead cancer cell line cells, induced to undergo apoptosis to mimic chemotherapy, up-regulation of pro-tumor gene expression was identified. Phagocytosis of apoptotic cancer cells by macrophages resulted in their transformation into tumor stem (initiating)-like cells, as indicated by the expression of epithelial markers (e.g., cytokeratin) and stem cell markers (e.g., Oct4) and their capability to differentiate in vitro and self-renew in serum-free media. Moreover, we identified a subset of monocytes/macrophages cells in the blood of cancer (breast, ovarian and colorectal) patients undergoing chemotherapy that harbor tumor transcripts. Our findings uncover a new role for macrophages in tumor development, where they can be transformed into tumor-like cells, potentially by horizontal gene transfer of tumor-derived genes, thus, by taking advantage of chemotherapy, these transformed macrophages promote tumor metastasis by escaping immune surveillance.
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