Peraldi Pascal, Ladoux Annie, Giorgetti-Peraldi Sophie, Dani Christian
Faculté de Médecine, Université Côte d'Azur, CNRS UMR7277, Inserm U1091, IBV, 06107 Nice, France.
Team Cellular and Molecular Physiopathology of Obesity, Université Côte d'Azur, Inserm, C3M, Bâtiment Universitaire ARCHIMED, 06204 Nice, France.
Cells. 2020 Oct 8;9(10):2251. doi: 10.3390/cells9102251.
Cancer associated fibroblasts (CAFs) are central elements of the microenvironment that control tumor development. In breast cancer, CAFs can originate from adipose progenitors (APs). We, and others, have shown that the primary cilium, an antenna-shaped organelle, controls several aspects of APs' biology. We studied the conversion of human APs into CAFs by breast cancer cell lines (BCCs). Deletion of the cilium of APs by a pharmacological inhibitor, or by siRNA, allow us to demonstrate that the cilium is necessary for the differentiation of APs into CAFs. BCCs increase production of TGF-β1 by APs, which is a known inducer of CAFs. Pharmacological inhibition of TGF-β1 signaling in APs prevents their conversion into CAFs. Since we previously showed that deletion of the APs' cilium inhibits TGF-β1 signaling, we propose that BCCs induce TGF-β1 production in Aps, which binds to the primary cilium of Aps and leads to their differentiation into CAFs. Inhibition of APs conversion into CAFs induces a loss in some of the biological effects of CAFs since deletion of the cilium of APs decreases their effect on the migration of BCCs. This is the first observation of a function of the cilium of APs in their conversion into CAFs, and its consequences on BCCs.
癌症相关成纤维细胞（CAFs）是控制肿瘤发展的微环境的核心要素。在乳腺癌中，CAFs可源自脂肪前体细胞（APs）。我们以及其他研究人员已表明，初级纤毛，一种天线状细胞器，控制着APs生物学的多个方面。我们研究了乳腺癌细胞系（BCCs）将人APs转化为CAFs的过程。通过药物抑制剂或小干扰RNA（siRNA）缺失APs的纤毛，使我们能够证明纤毛对于APs分化为CAFs是必需的。BCCs可增加APs产生转化生长因子-β1（TGF-β1），TGF-β1是一种已知的CAFs诱导剂。对APs中TGF-β1信号通路的药物抑制可阻止其转化为CAFs。由于我们之前表明缺失APs的纤毛会抑制TGF-β1信号通路，我们提出BCCs诱导APs产生TGF-β1，TGF-β1与APs的初级纤毛结合并导致其分化为CAFs。抑制APs转化为CAFs会导致CAFs的一些生物学效应丧失，因为缺失APs的纤毛会降低它们对BCCs迁移的影响。这是首次观察到APs的纤毛在其转化为CAFs过程中的功能及其对BCCs的影响。
