Studies of postpartum mammary gland involution reveal novel pro-metastatic mechanisms.
Studies of postpartum mammary gland involution reveal novel pro-metastatic mechanisms.
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DOI：
10.20517/2394-4722.2019.01
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Lyons, Traci R
中科院分区：
文献类型：
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作者：
Wallace, Taylor R;Tarullo, Sarah E;Lyons, Traci R
产后复旧是哺乳期乳腺在断奶后恢复到妊娠前状态的过程。肿瘤促进胶原蛋白的表达、基质金属蛋白酶的上调、M2巨噬细胞的浸润以及血液和淋巴管系统的重塑都是退化乳腺和乳腺肿瘤微环境共有的特征。退化乳腺的肿瘤促进性质可能最好地证明了产后乳腺癌（PPBC）的病例，或最近分娩后10年内诊断的病例。患有PPBC的女性比未经产的患者和产后窗口期外诊断的患者经历更侵袭性的疾病和更高的转移风险。脑信号蛋白7a（SEMA 7A）、环氧合酶-2（考克斯-2）和胶原蛋白都在退化的乳腺中表达，并且一起预测乳腺癌中降低的无转移存活率。研究这些蛋白质在退化中的作用对于了解它们对PPBC的贡献非常重要。因此，产后退化代表了一个有价值的模型，用于识别PPBC和经典癌症标志的新分子驱动因素。在这篇综述中，我们将强调退化和乳腺癌之间的相似性，并进一步定义SEMA 7A/考克斯-2/胶原蛋白相互作用对产后退化和乳腺肿瘤进展和转移的贡献。
Postpartum involution is the process by which the lactating mammary gland returns to the pre-pregnant state after weaning. Expression of tumor-promotional collagen, upregulation of matrix metalloproteinases, infiltration of M2 macrophages, and remodeling of blood and lymphatic vasculature are all characteristics shared by the involuting mammary gland and breast tumor microenvironment. The tumor promotional nature of the involuting mammary gland is perhaps best evidenced by cases of postpartum breast cancer (PPBC), or those cases diagnosed within 10 years of most recent childbirth. Women with PPBC experience more aggressive disease and higher risk of metastasis than nulliparous patients and those diagnosed outside the postpartum window. Semaphorin 7a (SEMA7A), cyclooxygenase-2 (COX-2), and collagen are all expressed in the involuting mammary gland and, together, predict for decreased metastasis free survival in breast cancer. Studies investigating the role of these proteins in involution have been important for understanding their contributions to PPBC. Postpartum involution thus represents a valuable model for the identification of novel molecular drivers of PPBC and classical cancer hallmarks. In this review, we will highlight the similarities between involution and cancer in the mammary gland, and further define the contribution of SEMA7A/COX-2/collagen interplay to postpartum involution and breast tumor progression and metastasis.