Cancer-associated fibroblasts contribute to cancer metastasis and apoptosis resistance in human ovarian cancer via paracrine SDF-1a

作者全名："Dai, Jie-min; Sun, Ke; Li, Chang; Cheng, Min; Guan, Jun-hua; Yang, Li-na; Zhang, Li-wen"

作者地址："[Dai, Jie-min; Sun, Ke; Li, Chang; Guan, Jun-hua; Yang, Li-na; Zhang, Li-wen] Fudan Univ, Shanghai Peoples Hosp 5, Dept Obstet & Gynecol, Shanghai 200240, Peoples R China; [Cheng, Min] Chongqing Med Univ, Dept Obstet & Gynecol, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Yang, LN; Zhang, LW (通讯作者)，Fudan Univ, Shanghai Peoples Hosp 5, Dept Obstet & Gynecol, Shanghai 200240, Peoples R China."

来源：CLINICAL & TRANSLATIONAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000906602300003

JCR分区：Q2

影响因子：2.8

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：CAFs; Tumor cell; SDF-1 alpha; Tumor metastasis; Chemoresistance

摘要："Background Cancer-associated fibroblasts (CAFs), one of the main members of stromal cells in tumor microenvironment are proposed to play a central role in promoting tumor metastasis. It is unclear whether and how CAFs mediates tumor metastasis or chemoresistance in human ovarian cancer. Methods CAFs were extracted from human ovarian cancer tissues (OCs) of patients with different kinds of histological types. Results We found that CAFs showed more aggressive potency than those tumor cells, both of which were isolated from the same ovarian cancer specimen. Moreover, when co-cultured with CAFs, cell migration abilities of ovarian cancer cells (SKOV3, OVCAR3 and HEY) were significantly increased. Next, we preliminarily detected a higher CAFs density in sections of metastatic lesions than those in primary tumor site of primary OCs clinically. However, no significant difference of stromal derived factors-1 alpha (SDF-1 alpha) production from CAFs was found between primary and metastatic lesions. Additionally, in contrast with tumor cells, CAFs exhibited obvious apoptosis resistance when treated with cisplatin. Furthermore, we found that cisplatin-induced cytotoxicity and apoptosis were significantly inhibited by co-cultured with recombinant human SDF-1 alpha in SKOV3 in a time and dose-dependent manner, and this effect was suppressed by the CXCR4 antagonist AMD3100. Conclusions CAFs might be involved in the malignant metastasis in human ovarian cancer through promoting cell migration in tumor cells. And their resistance to cytotoxic agents might be mediated by paracrine SDF-1 alpha/CXCR4 signaling in ovarian cancer."

基金机构：National Natural Science Foundation of China NSFC [81072120]; Chongqing Science and Technology Commission [cstc2017jcyjAX0194]; Fudan University [2019WYFY05]

基金资助正文："This work was supported by a grant from the National Natural Science Foundation of China (NSFC NO. 81072120), Chongqing Science and Technology Commission Project (cstc2017jcyjAX0194), Hospital-level Incubation Project of The Fifth People's Hospital of Shanghai, Fudan University (2019WYFY05)."