title: Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer.
abstract: Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the mechanisms underlying stromal fibroblast activation and their promotion of tumor growth remain largely unknown in gastric cancer. Here, we show that normal fibroblasts (NFs) from non-cancerous regions of gastric cancer exhibit the traits of CAFs when grown together with gastric cancer cells in vivo. Activation of NFs can be induced by co-culture with gastric cancer cells, while deprivation of hepatocyte growth factor (HGF) using a neutralizing antibody inhibits the activation of NFs. Moreover, we identify HGF as an important factor from CAFs that acts in a paracrine manner to promote tumorigenesis in vitro and in vivo. Taken together, these results suggest that HGF may play a pivotal role in the regulatory circuit between gastric cancer cells and stromal fibroblasts, and neutralization of HGF inhibits both activation and tumor-promoting properties of CAFs.
authors: Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, PR China.
authors: Xiongyan
authors: X
authors: Wu
authors: Xuehua
authors: X
authors: Chen
authors: Quan
authors: Q
authors: Zhou
authors: Pu
authors: P
authors: Li
authors: Beiqin
authors: B
authors: Yu
authors: Jianfang
authors: J
authors: Li
authors: Ying
authors: Y
authors: Qu
authors: Jun
authors: J
authors: Yan
authors: Yingyan
authors: Y
authors: Yu
authors: Min
authors: M
authors: Yan
authors: Zhenggang
authors: Z
authors: Zhu
authors: Bingya
authors: B
authors: Liu
authors: Liping
authors: L
authors: Su
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism; D018920:Coculture Techniques; D005347:Fibroblasts; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D047368:Tumor Burden; D059016:Tumor Microenvironment
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D034741:RNA, Small Interfering; D017228:Hepatocyte Growth Factor