转移
间质细胞
癌症研究
旁分泌信号
血管生成
外渗
肿瘤微环境
静脉注射
肿瘤进展
乳腺癌
癌细胞
生物
转录因子
癌症
内科学
医学
免疫学
肿瘤细胞
生物化学
受体
基因
作者
Samuel Seoane,Anxo Martínez-Ordóñez,Noemí Eiró,Pablo Cabezas-Sáinz,Lucía García‐Caballero,Luis O. González,Manuel Macı́a,Laura Sánchez,Francisco J. Vizoso,Román Pérez-Fernández
摘要
Abstract Cancer progression requires cells surrounding tumors be reeducated and activated to support tumor growth. Oncogenic signals from malignant cells directly influence stromal composition and activation, but the factors mediating this communication are still not well understood. We have previously shown that the transcription factor POU class 1 homeobox 1 (POU1F1), also known as Pit‐1, induces profound changes on neoplastic cell‐autonomous processes favoring metastasis in human breast cancer. Here we describe for the first time Pit‐1‐mediated paracrine actions on macrophages in the tumor microenvironment by using cell lines in vitro , zebrafish and mouse models in vivo , and samples from human breast cancer patients. Through the release of CXCL12, Pit‐1 in tumor cells was found to mediate the recruitment and polarization of macrophages into tumor‐associated macrophages (TAMs). In turn, TAMs collaborated with tumor cells to increase tumor growth, angiogenesis, extravasation and metastasis to lung. Our data reveal a new mechanism of cooperation between tumor cells and macrophages favoring metastasis and poor clinical outcome in human breast cancer, which suggests that Pit‐1 and CXCL12 should be further studied as potential prognostic and therapeutic indicators. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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