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Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis.

TitleTumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis.
Publication TypeJournal Article
Year of Publication1998
AuthorsCoughlin 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
JournalImmunity
Volume9
Issue1
Pagination25-34
Date Published1998 Jul
ISSN1074-7613
KeywordsAnimals, 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.

DOI10.1016/s1074-7613(00)80585-3
Alternate JournalImmunity
PubMed ID9697833
Grant ListT32 CA09140 / CA / NCI NIH HHS / United States

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