Discipline of Surgical Specialties, Adelaide Medical School, University of Adelaide, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia.
Robinson Research Institute, University of Adelaide, Adelaide, SA 5006, Australia.
Front Biosci (Landmark Ed). 2024 Sep 23;29(9):328. doi: 10.31083/j.fbl2909328.
Lactation is associated with long-term reduced risk of breast cancer. However, there is a transient increased risk of breast cancer in the 5 to 10 years postpartum and this is associated with a high incidence of metastasis and mortality. Breastmilk is a physiological fluid secreted by the mammary glands intimately connected with breast cells and the microenvironment that may affect postpartum breast cancer development and progression. This study aims to investigate the effect of breastmilk on interactions between breast cancer cells and macrophages .
Human breastmilk from healthy donors (n = 7) was pooled and incubated with breast cancer (MCF-7 and MDA-MB-231) and macrophage (RAW264.7) cell lines to assess cell proliferation, viability, migration, and expression of key genes associated with epithelial-mesenchymal transition (EMT) and macrophage phenotype. Indirect co-culture studies assessed the effect of breastmilk on interactions between breast cancer cells and macrophages.
Breastmilk increased the proliferation and viability of breast cancer cells, reduced EMT markers, and reduced cell migration in MDA-MB-231 cells. Breastmilk decreased mRNA expression of interleukin 1B (IL1B) and interleukin 10 (IL10) in macrophages. Reduced EMT marker expression was observed in breast cancer cells co-cultured with macrophages pre-treated with breastmilk. Macrophages co-cultured with breast cancer cells pre-treated with breastmilk exhibited increased expression of a pro-inflammatory cytokine tumor necrosis factor A (TNFA) and pro-inflammatory nitric oxide synthase 2 (NOS2), and reduced expression of cytokines IL10 and transforming growth factor B1 (TGFB1) which are associated with the alternatively-activated macrophage phenotype.
Breastmilk has the potential to promote breast cancer proliferation, however, it can also reduce breast cancer progression through inhibition of breast cancer cell migration and regulation of macrophage polarisation. These findings suggest that breastmilk has potential to shape the tumour microenvironment in postpartum breast cancer.
哺乳与乳腺癌长期风险降低相关。然而，产后 5-10 年内乳腺癌风险短暂增加，且与高转移率和高死亡率相关。母乳是乳腺分泌的一种生理液体，与乳腺细胞和微环境密切相关，可能影响产后乳腺癌的发展和进展。本研究旨在探讨母乳对乳腺癌细胞与巨噬细胞相互作用的影响。
从健康供体（n=7）中收集母乳，与乳腺癌（MCF-7 和 MDA-MB-231）和巨噬细胞（RAW264.7）细胞系共孵育，评估细胞增殖、活力、迁移和与上皮-间充质转化（EMT）和巨噬细胞表型相关的关键基因的表达。间接共培养研究评估了母乳对乳腺癌细胞与巨噬细胞相互作用的影响。
母乳增加了乳腺癌细胞的增殖和活力，降低了 MDA-MB-231 细胞中 EMT 标志物的表达，并减少了细胞迁移。母乳降低了巨噬细胞中白细胞介素 1B（IL1B）和白细胞介素 10（IL10）的 mRNA 表达。与未用母乳预处理的巨噬细胞共培养的乳腺癌细胞中，观察到 EMT 标志物表达减少。与用母乳预处理的乳腺癌细胞共培养的巨噬细胞表现出促炎细胞因子肿瘤坏死因子 A（TNFA）和促炎一氧化氮合酶 2（NOS2）表达增加，以及与替代激活的巨噬细胞表型相关的细胞因子 IL10 和转化生长因子 B1（TGFB1）表达减少。
母乳具有促进乳腺癌增殖的潜力，但也可以通过抑制乳腺癌细胞迁移和调节巨噬细胞极化来降低乳腺癌的进展。这些发现表明母乳有可能塑造产后乳腺癌的肿瘤微环境。
