title: Cancer-associated fibroblasts from hepatocellular carcinoma promote malignant cell proliferation by HGF secretion.
abstract: Cancer-associated fibroblasts (CAFs) are reported to support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion in most solid tumors. However, the roles of CAFs in the liver cancer microenvironment have not been thoroughly studied. In our previous study, we successfully isolated CAFs from hepatocellular carcinoma (HCC) (H-CAFs) and proved that H-CAFs suppressed the activation of NK cells and thereby created favorable conditions for HCC progression. In our present study, we found that the proliferation of MHCC97L and Hep3B cells was significantly promoted by treatment with conditioned medium from H-CAFs. Pathological analysis also revealed that H-CAFs increased the proportion of Ki-67 (+) malignant cells and prevented them from undergoing necrosis. Moreover, the concentration of hepatocyte growth factor (HGF) cytokine in the conditioned medium of H-CAFs was higher than conditioned medium from normal skin fibroblasts (NSFs). Anti-HGF significantly reduced the proliferation-promoting capability of H-CAFs. In addition, we found that the abundance of H-CAFs correlated positively with tumor size. These results indicate that H-CAFs are an important factor for promoting the growth of HCC in vitro and in vivo, and that HGF plays a key role in HCC proliferation induced by H-CAFs.
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Chang-Chang
authors.initials: CC
authors.lastname: Jia
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Bin-Sheng
authors.initials: BS
authors.lastname: Fu
authors.forename: XueFeng
authors.initials: X
authors.lastname: Hua
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Wang
authors.forename: Tuan-Jie
authors.initials: TJ
authors.lastname: Li
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Tai
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009336:Necrosis; D019899:Paracrine Communication; D047368:Tumor Burden
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor