Title | Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis. |
Publication Type | Journal Article |
Year of Publication | 1998 |
Authors | Coughlin CM, Salhany KE, Gee MS, LaTemple DC, Kotenko S, Ma X, Gri G, Wysocka M, Kim JE, Liu L, Liao F, Farber JM, Pestka S, Trinchieri G, Lee WM |
Journal | Immunity |
Volume | 9 |
Issue | 1 |
Pagination | 25-34 |
Date Published | 1998 Jul |
ISSN | 1074-7613 |
Keywords | Animals, Antineoplastic Agents, Female, Gene Expression, Interferon-gamma, Interleukin-12, Mammary Neoplasms, Experimental, Melanoma, Experimental, Mice, Mice, Inbred A, Mice, Inbred C3H, Mutagenesis, Neovascularization, Pathologic, Receptors, Interferon, Recombinant Proteins, Tumor Cells, Cultured |
Abstract | Expression of a dominant negative mutant IFNgammaR1 in murine SCK and K1735 tumor cells rendered them relatively unresponsive to IFNgamma in vitro and more tumorigenic and less responsive to IL-12 therapy in vivo. IL-12 induced histologic evidence of ischemic damage only in IFNgamma-responsive tumors, and in vivo Matrigel vascularization assays revealed that while IFNgamma-responsive and -unresponsive tumor cells induced angiogenesis equally well, IL-12 and its downstream mediator IFNgamma only inhibited angiogenesis induced by the responsive cells. IL-12 induced angiogenesis inhibitory activity in the responsive cells, which may be attributable to production of the chemokine IP-10. Thus, IL-12 and IFNgamma inhibit tumor growth by inducing tumor cells to generate antiangiogenic activity. |
DOI | 10.1016/s1074-7613(00)80585-3 |
Alternate Journal | Immunity |
PubMed ID | 9697833 |
Grant List | T32 CA09140 / CA / NCI NIH HHS / United States |
Submitted by mam2155 on March 24, 2014 - 4:16pm