CD206 modulates the role of M2 macrophages in the origin of metastatic tumors

Li, Hui; Miao, Ying-Qi; Suo, Li-Ping; Wang, Xi; Mao, Yi-Qing; Zhang, Xue-Hui; Zhou, Na; Tian, Jun-Rui; Yu, Xiu-Yan; Wang, Tong-Xia; Gao, Yan; Guo, Hong-Yan; Zhang, Zheng; Ma, Dian-Sheng; Wu, Hong-Xia; Cui, Yan-Wei; Zhang, Xi-Liang; Chi, Xiao-Chun; Li, Yu-Chi; Irwin, David M.; Niu, Gang; Tan, Huan-Ran

doi:10.7150/jca.91944

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International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

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J Cancer 2024; 15(5):1462-1486. doi:10.7150/jca.91944 This issue Cite

Research Paper

CD206 modulates the role of M2 macrophages in the origin of metastatic tumors

Hui Li^1†, Ying-Qi Miao^1†, Li-Ping Suo¹, Xi Wang¹, Yi-Qing Mao¹, Xue-Hui Zhang¹, Na Zhou¹, Jun-Rui Tian¹, Xiu-Yan Yu¹, Tong-Xia Wang², Yan Gao², Hong-Yan Guo², Zheng Zhang³, Dian-Sheng Ma⁴, Hong-Xia Wu⁴, Yan-Wei Cui⁴, Xi-Liang Zhang⁴, Xiao-Chun Chi⁵, Yu-Chi Li^6*✉, David M. Irwin^7*✉, Gang Niu^8*✉, Huan-Ran Tan^1*✉

1. Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
2. Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
3. Peking University First Hospital, Beijing, China.
4. Donggang Central Hospital, Donggang, China.
5. Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
6. Kellbenx Inc., Great River, NY, USA.
7. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
8. Beijing N&N Genetech Company, Beijing, China.
^† These authors contributed equally to this work and share first authorship: Hui Li, Ying-Qi Miao.
* These authors contributed equally to this work and are co-corresponding authors.

Citation:

Li H, Miao YQ, Suo LP, Wang X, Mao YQ, Zhang XH, Zhou N, Tian JR, Yu XY, Wang TX, Gao Y, Guo HY, Zhang Z, Ma DS, Wu HX, Cui YW, Zhang XL, Chi XC, Li YC, Irwin DM, Niu G, Tan HR. CD206 modulates the role of M2 macrophages in the origin of metastatic tumors. J Cancer 2024; 15(5):1462-1486. doi:10.7150/jca.91944. https://www.jcancer.org/v15p1462.htm

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Abstract

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.

Keywords: CD206, M2 macrophages, metastatic tumors, apoptosis, polarization

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APA

Li, H., Miao, Y.Q., Suo, L.P., Wang, X., Mao, Y.Q., Zhang, X.H., Zhou, N., Tian, J.R., Yu, X.Y., Wang, T.X., Gao, Y., Guo, H.Y., Zhang, Z., Ma, D.S., Wu, H.X., Cui, Y.W., Zhang, X.L., Chi, X.C., Li, Y.C., Irwin, D.M., Niu, G., Tan, H.R. (2024). CD206 modulates the role of M2 macrophages in the origin of metastatic tumors. Journal of Cancer, 15(5), 1462-1486. https://doi.org/10.7150/jca.91944.

ACS

Li, H.; Miao, Y.Q.; Suo, L.P.; Wang, X.; Mao, Y.Q.; Zhang, X.H.; Zhou, N.; Tian, J.R.; Yu, X.Y.; Wang, T.X.; Gao, Y.; Guo, H.Y.; Zhang, Z.; Ma, D.S.; Wu, H.X.; Cui, Y.W.; Zhang, X.L.; Chi, X.C.; Li, Y.C.; Irwin, D.M.; Niu, G.; Tan, H.R. CD206 modulates the role of M2 macrophages in the origin of metastatic tumors. J. Cancer 2024, 15 (5), 1462-1486. DOI: 10.7150/jca.91944.

NLM

CSE

Li H, Miao YQ, Suo LP, Wang X, Mao YQ, Zhang XH, Zhou N, Tian JR, Yu XY, Wang TX, Gao Y, Guo HY, Zhang Z, Ma DS, Wu HX, Cui YW, Zhang XL, Chi XC, Li YC, Irwin DM, Niu G, Tan HR. 2024. CD206 modulates the role of M2 macrophages in the origin of metastatic tumors. J Cancer. 15(5):1462-1486.

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