Abstract:
Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer and shows high metastatic potential. Macrophages (or known as tumor-associated macrophages, TAM) play an important role in promoting TNBC metastasis. Breast cancer as a solid tumor often exists in a hypoxic tumor microenvironment. Hypoxia promotes cancer cell metastasis, but the role of macrophages in promoting tumor metastasis in a hypoxic environment is still unclear. THP1 cells were differentiated into TAM and cultured in hypoxia. The migration ability of the TNBC cells BT-549 and MDA-MB-231 induced by TAM was detected through Transwell. MDA-MB-231 was transplanted through tail vein into the nude mice and the organ metastasis ability of TNBC cells induced by TAM was analyzed through CT scan. The effect of hypoxia on the secretion of several factors related to tumor metastasis in TAM was detected with the ELISA test. The difference between CCL22 receptor CCR4 and other CCR expression in breast cancer tissues and normal tissues was analyzed with the GDSC online software. The results showed that hypoxia-induced TAM significantly enhanced the migration of TNBC cells. Hypoxia induced CCL22 expression in TAM. Moreover, CCR4 expression in breast cancer tissues was significantly higher than that in normal tissues. In conclusion, TAM could promote the migration of TNBC cells through secretion of CCL22 under hypoxia.