ITGA7 loss drives the differentiation of adipose-derived mesenchymal stem cells to cancer-associated fibroblasts

作者全名："Liu, Xiaoli; Gao, Rui; Wu, Qiulei; Li, Guoqing; Xu, Xiaohan; Li, Wenhan; Liu, Pan; Wang, Xiaoman; Cai, Jing; Li, Min; Wang, Zehua"

作者地址："[Liu, Xiaoli; Gao, Rui; Wu, Qiulei; Li, Guoqing; Xu, Xiaohan; Li, Wenhan; Liu, Pan; Wang, Xiaoman; Cai, Jing; Wang, Zehua] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Obstet & Gynecol, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China; [Li, Min] Chongqing Med Univ, Affiliated Hosp 2, Ctr Reprod Med, Obstet & Gynecol Dept, Chongqing 400010, Peoples R China"

通信作者："Wang, ZH (通讯作者)，Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Obstet & Gynecol, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China.; Li, M (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Ctr Reprod Med, Obstet & Gynecol Dept, Chongqing 400010, Peoples R China."

来源：MOLECULAR CARCINOGENESIS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001136374800001

JCR分区：Q2

影响因子：3

年份：2024

卷号：63

期号：3

开始页：479

结束页：493

文献类型：Article; Early Access

关键词：integrin; mesenchymal stem cells; metastasis; multilineage differentiation; ovarian cancer

摘要："Cancer-associated fibroblasts (CAFs) represent a major cellular component of the tumor (pre-)metastatic niche and play an essential role in omental dissemination of ovarian cancer. The omentum is rich in adipose, and adipose-derived mesenchymal stem cells (ADSCs) have been identified as a source of CAFs. However, the molecular events driving the phenotype shift of ADSCs remain largely unexplored. In this research, we focus on integrins, transmembrane receptors that have been widely involved in cellular plasticity. We found that integrin alpha 7 (ITGA7) was the only member of the integrin family that positively correlated with both overall survival and progression-free survival in ovarian cancer through GEPIA2. The immunohistochemistry signal of ITGA7 was apparent in the tumor stroma, and a lower omental ITGA7 level was associated with metastasis. Primary ADSCs were isolated from the omentum of patients with ovarian cancer and identified by cellular morphology, biomarkers, and multilineage differentiation. The conditional medium of ovarian cancer cells induced ITGA7 expression decrease and phenotypic changes in ADSCs. Downregulation of ITGA7 in primary omental ADSCs led to decrease in stemness properties and emerge of characteristic morphology and biomarkers of CAFs. Moreover, the conditioned medium of ADSCs with ITGA7 depletion exhibited enhanced abilities to improve the migration and invasion of ovarian cancer cells in vitro. Overall, these findings indicate that loss of ITGA7 may induce the differentiation of ADSCs to CAFs that contribute to a tumor-supportive niche."

基金机构：National Natural Science Foundation of Hubei province; [2022CFB107]

基金资助正文：This research was funded by the National Natural Science Foundation of Hubei province (grant number 2022CFB107).