癌症研究
刺猬
乳腺癌
肿瘤微环境
癌细胞
生物
癌症
刺猬信号通路
巨噬细胞
化学
细胞生物学
信号转导
医学
内科学
体外
生物化学
肿瘤细胞
作者
Xiaojun Xu,Jiabao Ye,Cheng Huang,Yuchun Yan,Jun Li
标识
DOI:10.1016/j.taap.2018.12.013
摘要
Hedgehog (Hh) pathway hyperactivation has been observed in various tumors, including breast cancer, and Hh pathway inhibitors have demonstrated antitumor activity in breast cancer. The tumor microenvironment (TME) has been shown to play an important role in modulating cancer cell drug sensitivity, but the TME response to Hh pathway inhibitors is unclear. In the current study, we observed increased TME infiltration of macrophages in breast cancer tissue, and specifically, M2 polarized macrophages after neoadjuvant chemotherapy. Furthermore, we observed an enhanced tolerance to Hh pathway inhibitors in MDA-MB-231 cells after co-culturing with M2 macrophages. In addition, we demonstrated that Hh pathway inhibition significantly induced IL6 expression, and validated that the tolerance to Hh pathway inhibitors was IL6-dependent. This study demonstrates a role of macrophages in Hh pathway inhibition resistance and a role of macrophage-derived IL6 in this resistance of breast cancer cells to Hh inhibition. These data indicate that antagonizing IL6 together with Hh pathway inhibitors may be a novel therapeutic strategy for breast cancer.
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