癌相关成纤维细胞
间质细胞
前列腺癌
肿瘤微环境
循环肿瘤细胞
癌症研究
癌细胞
癌症
肿瘤进展
成纤维细胞活化蛋白
医学
病理
转移
内科学
作者
Nerymar Ortiz-Otero,Andrea B. Clinch,Jacob M. Hope,Wenjun Wang,Cynthia A. Reinhart‐King,Michael R. King
出处
期刊:Oncotarget
[Impact Journals, LLC]
日期:2020-03-24
卷期号:11 (12): 1037-1050
被引量:64
标识
DOI:10.18632/oncotarget.27510
摘要
Previous studies have demonstrated that CTCs do not travel in the bloodstream alone, but rather are accompanied by clusters of stromal cells such as cancer associated fibroblasts (CAFs). Our laboratory has confirmed the presence of CAFs in the peripheral blood of prostate cancer (PC) patients. The observation that CAFs disseminate with CTCs prompts the examination of the role of CAFs in CTC survival under physiological shear stress during the dissemination process using a clinically relevant, three-dimensional (3D) co-culture model. In this study, we found that "reactive CAFs" induce shear resistance to prostate tumor cells via intercellular contact and soluble derived factors. In addition, these reactive CAFs conserve the proliferative capability of tumor cells in the presence of high magnitude fluid shear stress (FSS). This reactive CAF phenotype emerges from normal fibroblasts (NF), which take on the CAF phenotype when co-cultured with tumor cells. The reactive CAFs showed higher expression of α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) compared to differentiated CAFs, when co-cultured with PC cells at the same experimental conditions. Together, we found that the activation mechanism of NF to CAF comprises different stages that progress from a reactive to quiescent cellular state in which these two states are differentiated by the fluctuation of intensity in CAF markers. Here we determined that a reactive state of CAFs proved to be important for supporting tumor cell survival and proliferation. These findings suggest the use of CAFs as a marker for cancer progression and a potential target for novel cancer therapeutics to treat metastatic disease.
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