The immune environment of the mammary gland fluctuates during post-lactational regression and correlates with tumour growth rate.
The immune environment of the mammary gland fluctuates during post-lactational regression and correlates with tumour growth rate.
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DOI：
10.1242/dev.200162
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发表时间：
2022-04-15
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影响因子：
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哺乳期后乳腺退化包括广泛的程序性细胞死亡和产奶上皮细胞的去除，细胞外基质成分的分解和间质脂肪细胞的重新分化。这种高度调节的退化过程与女性乳腺癌风险的一过性增加有关。使用同基因肿瘤模型，我们发现肿瘤生长明显改变，这取决于肿瘤细胞被植入的退化阶段。在退化的第3天注射的肿瘤细胞比那些未分娩的小鼠生长得更快，而在退化的第6天开始的肿瘤生长明显慢。肿瘤进展的这些差异与先天免疫细胞的明显变化有关，特别是在表达F4/80的巨噬细胞和TCRδ+非常规T细胞之间。在第一次怀孕的老年母亲中，怀孕后乳腺癌的风险会加剧，在我们的模型中，与年轻小鼠相比，老年小鼠最初的肿瘤生长速度略快。我们的研究结果对乳腺癌的风险和产后乳腺癌的抗炎治疗有一定的指导意义。摘要：乳腺退化与免疫细胞类型和数量在不同阶段的动态变化有关，而免疫细胞类型和数量的动态变化与移植瘤细胞的初始生长速度有关。
Post-lactational mammary gland regression encompasses extensive programmed cell death and removal of milk-producing epithelial cells, breakdown of extracellular matrix components and redifferentiation of stromal adipocytes. This highly regulated involution process is associated with a transient increased risk of breast cancer in women. Using a syngeneic tumour model, we show that tumour growth is significantly altered depending on the stage of involution at which tumour cells are implanted. Tumour cells injected at day 3 involution grew faster than those in nulliparous mice, whereas tumours initiated at day 6 involution grew significantly slower. These differences in tumour progression correlate with distinct changes in innate immune cells, in particular among F4/80-expressing macrophages and among TCRδ+ unconventional T cells. Breast cancer post-pregnancy risk is exacerbated in older first-time mothers and, in our model, initial tumour growth is moderately faster in aged mice compared with young mice. Our results have implications for breast cancer risk and the use of anti-inflammatory therapeutics for postpartum breast cancers. Summary: Mammary gland involution is associated with dynamic changes in immune cell types and numbers at different stages that correlates with the initial rate of growth of implanted tumour cells.
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DOI：
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发表时间：
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