title: bFGF Promotes Migration and Induces Cancer-Associated Fibroblast Differentiation of Mouse Bone Mesenchymal Stem Cells to Promote Tumor Growth.
abstract: Tumors recruit bone mesenchymal stem cells (BMSCs) to localize to tumor sites, which induces their conversion into cancer-associated fibroblasts (CAFs) that facilitate tumor progression. However, this process is poorly understood on the molecular level. In this study, we found that 4T1 breast cancer cells promoted the migration of BMSCs, and bFGF neutralizing antibody inhibited the migration of BMSCs induced by a tumor-conditioned medium. In addition, exogenous bFGF enhanced the migration of BMSCs in a dose-dependent manner in vitro. Furthermore, BMSCs promoted the proliferation of 4T1 tumor cells under BMSC-conditioned medium and in tumor xenograft model. Dramatically, BMSCs expressed CAF markers and produced collagen in the tumor microenvironment, and this transition was blocked by bFGF antibody. In addition, exogenous bFGF induced CAF differentiation of BMSCs. And bFGF increased phosphorylation of Erk1/2 and Smad3 in BMSCs and Erk inhibitor PD98059 was shown to block bFGF-induced Erk and Smad3 phosphorylation, suggesting that Erk/Smad3 signaling pathway involved in BMSC transdifferentiation induced by bFGF. Collectively, our results indicate that bFGF signaling plays indispensable roles in BMSC recruitment and transdifferentiation into CAFs and the consequent protumor effects, and targeting tumor stroma through bFGF inhibition maybe a promising strategy to suppress tumor progression.
authors.affiliation: 1 Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: 1 Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
authors.forename: Jian
authors.initials: J
authors.lastname: Hao
authors.affiliation: 1 Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
authors.forename: Yu
authors.initials: Y
authors.lastname: Mao
authors.affiliation: 2 Tianjin Medical University , Tianjin, China .
authors.forename: Zi-Qi
authors.initials: ZQ
authors.lastname: Jin
authors.affiliation: 1 Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
authors.forename: Rui
authors.initials: R
authors.lastname: Cao
authors.affiliation: 3 Zhong-Shan-Men In-Patient Department, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
authors.forename: Cui-Hong
authors.initials: CH
authors.lastname: Zhu
authors.affiliation: 1 Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Liu
authors.affiliation: 3 Zhong-Shan-Men In-Patient Department, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: 1 Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Ding
authors.affiliation: 4 Tianjin Medical University General Hospital , Tianjin, China .
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: 2 Tianjin Medical University , Tianjin, China .
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: 1 Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
authors.forename: Xiong-Zhi
authors.initials: XZ
authors.lastname: Wu
keywords: bFGF; bone mesenchymal stem cells; breast cancer; cancer-associated fibroblasts; differentiation; migration