title: Overexpression of HIF-1α in primary gallbladder carcinoma and its relation             to vasculogenic mimicry and unfavourable prognosis.
abstract: As a novel mode of tumor neovascularization, vasculogenic mimicry (VM) has been reported to increase tumor-related mortality in many different solid tumors. In the present study, two established human gallbladder carcinoma (GBC) cell lines (highly aggressive GBC-SD and poorly aggressive SGC-996) cultured on a three-dimensional matrix were assessed for the ability of VM channel formation under normoxic or hypoxic conditions. In addition, the relationship between HIF-1α gene expression and VM channel formation of GBC cells in vitro was measured using the small interfering RNA (siRNA) technique, western blotting and real-time reverse transcription (RT)-PCR analysis. Furthermore, H&E and CD31/periodic acid-Schiff (PAS) staining were used to observe VM in GBC tissue samples. Additionally, all seventy-one specimens with VM and non-VM were stained for hypoxia inducible factor-1 α (HIF-1α) and its correlation with clinicopathological features and prognosis was analyzed simultaneously. We found that hypoxia could induce more VM channel formation and elevated HIF-1α expression in highly aggressive GBC-SD cells. HIF-1α siRNA efficiently knocked down HIF-1α expression and GBC VM networks under either normoxic or hypoxic conditions. VM was present in human primary GBC and overexpression of HIF-1α was significantly correlated with depth of invasion and perineural involvement in the non-VM group. Moreover, VM and HIF-1α were independent factors for the overall survival of GBC patients and correlated with decreased survival. In conclusion, VM was present in human GBC. As a critical mediator in VM formation, high expression of HIF-1α was associated with VM and tumor progression in GBC patients.
authors.affiliation: Department of Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Shen
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yue-Zu
authors.initials: YZ
authors.lastname: Fan
authors.forename: Wen-Zhong
authors.initials: WZ
authors.lastname: Zhang
authors.forename: Jing-Tao
authors.initials: JT
authors.lastname: Zhang
authors.forename: Xing-Sui
authors.initials: XS
authors.lastname: Lu
authors.forename: Chun
authors.initials: C
authors.lastname: Ye
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005260:Female; D005706:Gallbladder Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering