Tumacrophage: macrophages transformed into tumor stem-like cells by virulent genetic material from tumor cells

// Yizhuang Zhang 1, * , Na Zhou 1, * , Xiuyan Yu 1, * , Xuehui Zhang 1 , Shanxin Li 1 , Zhen Lei 5 , Ruobi Hu 1 , Hui Li 1 , Yiqing Mao 1 , Xi Wang 1 , Jinshu Zhang 2 , Yuan Li 3 , Hongyan Guo 3 , David M. Irwin 4 , Gang Niu 5 and Huanran Tan 1 1 Department of Pharmacology, Peking University, Beijing, China 2 Department of Clinical Laboratory, The 305 Hospital of People’s Liberation Army, Beijing, China 3 Department of Gynaecology and Obstetrics, Peking University Third Hospital, Beijing, China 4 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada 5 N & N Genetech Company, Ltd., Beijing, China * These authors have contributed equally to this work Correspondence to: Huanran Tan, email: tanlab@bjmu.edu.cn Gang Niu, email: nngene@sohu.com David M. Irwin, email: david.irwin@utoronto.ca Keywords: macrophages, circulating tumor cells, apoptosis, phagocytosis, epithelial tumors Received: May 04, 2017      Accepted: June 20, 2017      Published: July 18, 2017 ABSTRACT 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.