M2 macrophages are the origin of tumor metastasis

Abstract Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have been focusing on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we propose a novel mode for cancer metastasis. Here 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 genes are induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source of the distal tissue tumor metastasis. This conclusion is supported by the presence of fused cells with both macrophage and tumor cell characteristics in the peripheral blood and ascites of patients with ovarian cancer. By suppressing the expression of CD206 in M2 macrophages by siRNA, we show that the growth and metastasis of tumors is suppressed at the in vitro cell line and in the in vivo experimental mice models. In summary, we show that M2 macrophages in the blood circulation undergo a "change of loyalty" to become "cancer cells" that undergo distal tissue metastasis, which can be suppressed by the knockdown of CD206 expression.