SLAMF8 Promotes M2 Polarization of Macrophages and Enhances Breast Cancer Proliferation.

BACKGROUND: Breast cancer is characterized by a complex pathogenesis and diverse clinical manifestations. Tumor-associated macrophages (TAMs) play a pivotal role in tumorigenesis, metastasis, and response to anticancer therapies. This study aimed to analyze the functional role of signaling lymphocytic activation molecule family 8 (SLAMF8) in TAMs and its impact on breast cancer cell proliferation. METHODS: The SLAMF8 silencing in THP-1 cells was established by transfection with SLAMF8 shRNA lentiviral particles, and the THP-1 cells were induced to M0 macrophages or M2 macrophages. The M2 macrophage markers, CD11b+CD163, CD206, and IL-10, were measured by flow cytometry and Western blotting. The induced macrophages were cocultured with breast cancer cells (MCF-7 and MDA-MB-231) using a transwell insert. The viability and migration of cancer cells were measured using CCK-8 and transwell migration. The STAT6 and NF-κB pathways were measured using Western blotting. In vivo, mice were co-injected with breast cancer cells and the THP-1-derived macrophages to observe the tumor growth. The NF-κB pathway in tumor tissues was measured by immunohistochemistry and Western blotting. RESULTS: The SLAMF8 silencing significantly downregulated the number of THP-1-derived M2 macrophages. The viability, migration, and the STAT6 and NF-κB pathways of breast cancer cells were significantly enhanced after co-culture with M2 macrophages compared to co-culture with M0 macrophages. However, the SLAMF8 silencing markedly suppressed the promoting effects of M2 macrophage co-culture on the above factors in cancer cells. In line with the in-vitro results, co-injection with M2 macrophages significantly promoted the tumor growth. Moreover, the SLAMF8 silencing in M2 macrophages downregulated the tumor growth compared with that of cancer cells co-injected with M2 macrophages without SLAMF8 silencing. CONCLUSION: This study showed that SLAMF8 silencing downregulated M2 macrophage polarization and weakened the promoting effects of M2 macrophages on breast cancer cells, suggesting a promising therapeutic strategy for breast cancer.