Lappano Rosamaria, Maggiolini Marcello
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
J Steroid Biochem Mol Biol. 2018 Feb;176:49-56. doi: 10.1016/j.jsbmb.2017.02.019. Epub 2017 Feb 27.
The aggressiveness of breast tumors is deeply influenced by the surrounding stroma. In this regard, the functional crosstalk between cancer cells and the tumor microenvironment has received considerable attention in recent years. Cancer-associated fibroblasts (CAFs) are active components of the tumor stroma as they play a main role in the initiation, progression, metastasis and recurrence of breast malignancy. Hence, a better understanding of the mechanisms through which host stroma may contribute to cancer development would lead to novel therapeutic approaches aimed to target both tumor cells and the adjacent microenvironment. The G protein estrogen receptor (GPER/GPR30) has been involved in estrogenic signaling in normal and malignant cells, including breast cancer. It is noteworthy that the potential of GPER to mediate stimulatory effects of estrogens has been also shown in CAFs derived from patients with breast tumors, suggesting that GPER may act at the cross-road between cancer cells and these important components of the tumor microenvironment. This review recapitulates recent findings underlying the breast tumor-promoting action of CAFs, in particular their functional liaison with breast cancer cells via GPER toward the occurrence of malignant features.
乳腺肿瘤的侵袭性深受周围基质的影响。在这方面，癌细胞与肿瘤微环境之间的功能性相互作用近年来受到了相当多的关注。癌症相关成纤维细胞（CAFs）是肿瘤基质的活跃成分，因为它们在乳腺恶性肿瘤的起始、进展、转移和复发中起主要作用。因此，更好地理解宿主基质可能促进癌症发展的机制，将导致旨在靶向肿瘤细胞和邻近微环境的新型治疗方法。G蛋白雌激素受体（GPER/GPR30）已参与正常细胞和恶性细胞（包括乳腺癌细胞）中的雌激素信号传导。值得注意的是，在源自乳腺肿瘤患者的CAFs中也显示出GPER介导雌激素刺激作用的潜力，这表明GPER可能在癌细胞与肿瘤微环境的这些重要成分之间的交叉点发挥作用。本综述总结了近期关于CAFs促进乳腺肿瘤作用的研究发现，特别是它们通过GPER与乳腺癌细胞在恶性特征发生方面的功能联系。
