Macrophage CCL22 Secretion Under Hypoxic Conditions Promotes the Metastasis of Triple-Negative Breast Cancer

Abstract

Objective: To explore the mechanism by which macrophages secrete CCL22 to promote the metastasis of triple-negative breast cancer under hypoxic conditions. Methods: 20 ng/mL mass concentration of phorbol 12-myristate 13-acetate (PMA) cell culture medium, 4?,6-diamidino-2-phenylindole (DAPI), dimethyl sulfoxide (DMSO), trypsin digestion solution, CCL18 Kit , Interleukin (IL)-10 Kit, CCL17 Kit, CCL22 Kit, TRIzolTM Reagent Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Kit, triple-negative breast cancer cells MDA-MB-231 and BT-549, as well as other reagents were used to culture triple-negative breast cancer (TNBC) cells MDA-MB-231 and BT-549 as well as human mononuclear cells THP-1, analyze and observe the metastasis of triple-negative breast cancer cells to the lungs, the secretion of CCL22, the migration of triple-negative breast cancer, and the situation of CCR4. Results: Compared with normal tumor-associated macrophage (TAM), hypoxic TAM further promoted the migration of tumor cells. The number of tumor metastases in the lungs, induced by hypoxic TAM, was significantly higher than that of normoxic TAM. Hypoxia can significantly stimulate the expression of CCL22. CCL22 can significantly promote the migration of MDA-MB-231 and BT-549 cells. The expressions of CCR3, CCR4, and CCR5 in tumor tissues were significantly increased compared with normal tissues, in which CCR4 showed the most significant increase. Conclusion: TAM cultured under hypoxia significantly enhanced the migration ability of TNBC cells and promoted the metastasis of cancer cells to the lungs in vivo. The hypoxic condition induced TAM to secrete CCL22; the expression of CCL22 receptor, CCR4, in breast cancer tissues was significantly higher than that in normal tissues.