title: Aberrant expression of B7-H3 in gastric adenocarcinoma promotes cancer cell metastasis.
abstract: B7-H3 belongs to the B7 superfamily, a group of molecules that costimulate or downmodulate T cell responses. Although it has been shown that B7-H3 can inhibit T cell responses, several studies, most of them performed in murine systems, found B7-H3 to act in a co-stimulatory manner. In addition, B7-H3 is also expressed in various human cancers and is correlated with the poor outcome of cancer patients. The functional role of B7-H3 in cancer is still controversially discussed. In the present study, we compared B7-H3 expression in normal gastric tissues and gastric cancer tissue specimens and determined the effects of low B7-H3 expression on the human gastric cancer cell line SGC-7901 by using RNAi. B7-H3 expression in gastric specimens was determined by tissue qPCR and immunohistochemisty. A SGC-7901 cell line with low B7-H3 expression was established by lentiviral-mediated RNA interference to investigate the effect of B7-H3 on cancer cell migration and invasion in vitro. By establishing an orthotopic transplantation gastric cancer mouse model, the effect of B7-H3 on cell migration and invasion was studied in vivo. B7-H3 expression was significantly higher in the gastric cancer group than that in the normal gaster group. B7-H3 knockdown by RNA interference decreased cell migration and Transwell invasion up to 50% in vitro. In the orthotopic transplantation gastric cancer mouse model, the effect of inhibiting metastasis by knockdown of B7-H3 was assessed in terms of the average postmortem abdominal visceral metastatic tumor weight. The results revealed that inhibition of B7-H3 expression reduced gastric cancer metastasis in vivo. In conclusion, B7-H3 is aberrantly expressed in gastric cancer. In addition to modulating tumor immunity, B7-H3 may have a novel role in regulating SGC-7901 cell metastasis.
authors.affiliation: Department of General Surgery, The First People's Hospital of Wujiang, Wujiang, Jiangsu 215200, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of General Surgery, The First People's Hospital of Wujiang, Wujiang, Jiangsu 215200, P.R. China.
authors.forename: Genhai
authors.initials: G
authors.lastname: Shen
authors.affiliation: Department of General Surgery, The First People's Hospital of Wujiang, Wujiang, Jiangsu 215200, P.R. China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, The First People's Hospital of Wujiang, Wujiang, Jiangsu 215200, P.R. China.
authors.forename: Quangen
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D060887:B7 Antigens / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D060887:B7 Antigens; C423237:CD276 protein, human