|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|
|Date Published||1998 Jul|
|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|
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.
|Grant List||T32 CA09140 / CA / NCI NIH HHS / United States|