title: Galectin-1 mediates TGF-β-induced transformation from normal fibroblasts into carcinoma-associated fibroblasts and promotes tumor progression in gastric cancer.
abstract: Rcinoma-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment. Cancer cells can induce the transformation from normal fibroblasts (NFs) into CAFs, reciprocally, CAFs promote tumor invasion and proliferation. TGF-β has been the mostly accepted factor to fuel NFs transformation into CAFs. Galectin-1 (Gal1) is highly upregulated in CAFs of multiple human cancers, and overexpression of Gal1 in CAFs promotes tumor progression. The effect of Gal1 on TGF-β-induced CAFs activation has not yet been established in gastric cancer (GC). In this study, we show that Gal1 expression in stroma is positively related to TGF-β in epithelial cells by retrospective analysis of GC patient samples. Meanwhile, conditioned media (CMs) from gastric cancer cells induce expression of both Gal1 and the CAFs marker alpha smooth muscle actin (α-SMA) in NFs via TGF-β secretion. Knockdown of Gal1 prevents TGF-β-induced the conversion of NFs to CAFs. CMs from fibroblasts overexpressing Gal1 inhibits cancer cells apoptosis, promotes migration and invasion in vitro. Thus, Gal1 is significantly involved in the development of tumor-promoting microenvironment by enhancing TGF-β signaling in a positive feedback loop. Targeting Gal1 in tumor stroma should be considered as a potential therapeutic target for GC.
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang, China.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Guan
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang, China.
authors.forename: Xingyun
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Clinical Research Center, The Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou, Zhejiang, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang, China.
authors.forename: Lisong
authors.initials: L
authors.lastname: Teng
keywords: Stric cancer; TGF-β; carcinoma-associated fibroblast; galectin-1; normal fibroblast; transformation