title: Expression of the Mig (CXCL9) gene in murine lung carcinoma cells generated angiogenesis-independent antitumor effects.
abstract: We examined whether expression of monokine induced by IFN-gamma (Mig, CXCL9) in tumors could produce antitumor effects. Murine lung carcinoma cells (A11) were retrovirally transduced with the murine Mig gene (A11/Mig) and were inoculated into syngeneic mice. Although proliferation in vitro of A11/Mig cells was not different from that of parent cells, the growth in vivo of A11/Mig tumors was significantly retarded compared with that of parent tumors. The antitumor effect was dependent on the amount of Mig produced. We compared the expression level of marker genes of lymphocytes and endothelial cells between parent and A11/Mig tumor masses with reverse transcription-polymerase chain reaction. Expression of CD4, CD8alpha, CD40, CD86, CD28, CD31 and vascular endothelial growth factor was not different between the two tumor groups but expression of CD40 ligand, CD80, NK1.1 and CXCR3 was relatively lower in A11/Mig tumors. Although Mig is a chemotactic factor for activated T and NK cells and an inhibitor for angiogenesis, the present data suggested that production of Mig in tumors did not recruit activated T and NK cells efficiently or suppress angiogenesis. The antitumor effects by Mig could be independent of anti-angiogenesis and recruitment of T and NK cells.
authors.affiliation: Division of Pathology, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Wang
authors.forename: Akihiko
authors.initials: A
authors.lastname: Wada
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Ugai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tagawa
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000517:prevention & control*; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology; D008175:Lung Neoplasms / Q000098:blood supply / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma