title: Hedgehog Signaling Activation in Hepatic Stellate Cells Promotes Angiogenesis and Vascular Mimicry in Hepatocellular Carcinoma.
abstract: Previous studies have established that hedgehog (Hh) signaling mediates tumor-stroma interaction and promotes hepatocellular carcinoma progression. Here, we demonstrated that activation of Hh signaling in hepatic stellate cell (HSC) line LX-2 by Huh-7-derived sonic Hh led to increased secretion of angiogenic factors and promoted angiogenesis in vitro. The activated LX-2 also enhanced vascular mimicry of hepatoma cells. Furthermore, co-injection of Huh-7 and LX-2 significantly accelerated tumor growth with enhanced angiogenesis compared with Huh-7 alone, which could be partly abrogated by Hh signaling inhibitor. Collectively, our data showed that paracrine Hh signaling mediated pro-angiogenic function of HSC and enhanced hepatoma growth.
authors.affiliation: a Department of Surgical Oncology , Xianyang Hospital of Yan'an University , Xianyang, Shannxi , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: a Department of Surgical Oncology , Xianyang Hospital of Yan'an University , Xianyang, Shannxi , China.
authors.forename: Shuanlin
authors.initials: S
authors.lastname: Miao
authors.affiliation: a Department of Surgical Oncology , Xianyang Hospital of Yan'an University , Xianyang, Shannxi , China.
authors.forename: Manyuan
authors.initials: M
authors.lastname: Miao
authors.affiliation: a Department of Surgical Oncology , Xianyang Hospital of Yan'an University , Xianyang, Shannxi , China.
authors.forename: Renshuan
authors.initials: R
authors.lastname: Li
authors.affiliation: a Department of Surgical Oncology , Xianyang Hospital of Yan'an University , Xianyang, Shannxi , China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Cao
authors.affiliation: a Department of Surgical Oncology , Xianyang Hospital of Yan'an University , Xianyang, Shannxi , China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: a Department of Surgical Oncology , Xianyang Hospital of Yan'an University , Xianyang, Shannxi , China.
authors.forename: Genzuan
authors.initials: G
authors.lastname: Huang
authors.affiliation: a Department of Surgical Oncology , Xianyang Hospital of Yan'an University , Xianyang, Shannxi , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Fu
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D053823:Hedgehog Proteins / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D015398:Signal Transduction; D047368:Tumor Burden
chemical_list: D043925:Angiogenesis Inducing Agents; D053823:Hedgehog Proteins; D008024:Ligands
keywords: Angiogenesis; Hedgehog signaling; Hepatic stellate cells; Hepatocellular carcinoma; Vascular mimicry