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

TY - JOUR

T1 - Tumor cell responses to IFNγ affect tumorigenicity and response to IL- 12 therapy and antiangiogenesis

AU - Coughlin, Christina M.

AU - Salhany, Kevin E.

AU - Gee, Michael S.

AU - LaTemple, Denise C.

AU - Kotenko, Serguei

AU - Ma, Xiao Jing

AU - Gri, Giorgia

AU - Wysocka, Maria

AU - Kim, Ji Eun

AU - Liu, Li

AU - Liao, Fang

AU - Farber, Joshua M.

AU - Pestka, Sidney

AU - Trinchieri, Giorgio

AU - Lee, William M.F.

N1 - Funding Information: The authors wish to thank Scott Wright (The Wistar Institute), David Sehy, and Sally Sarawar (PharMingen) for their assistance and the Genetics Institute for recombinant murine IL-12. C. M. C. and M. S. G. are supported by a Medical Scientist Training Program grant from the NIH. K. E. S. is supported by awards from the NIH and the University of Pennsylvania Department of Pathology. D. C. L. is supported by NIH training grant T32 CA09140. S. P. and S. K. are supported by awards from the NIH and the American Cancer Society. W. M. F. L., G. T., G. G., X. M., and M. W. are supported by awards from the NIH.

PY - 1998/7

Y1 - 1998/7

N2 - Expression of a dominant negative mutant IFNγR1 in murine SCK and K1735 tumor cells rendered them relatively unresponsive to IFNγ in vitro and more tumorigenic and less responsive to IL-12 therapy in vivo. IL-12 induced histologic evidence of ischemic damage only in IFNγ-responsive tumors, and in vivo Matrigel vascularization assays revealed that while IFNγ-responsive and -unresponsive tumor cells induced anglogenesis equally well, IL-12 and its downstream mediator IFNγ, 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 IFNγ, inhibit tumor growth by inducing tumor cells to generate antiangiogenic activity.

AB - Expression of a dominant negative mutant IFNγR1 in murine SCK and K1735 tumor cells rendered them relatively unresponsive to IFNγ in vitro and more tumorigenic and less responsive to IL-12 therapy in vivo. IL-12 induced histologic evidence of ischemic damage only in IFNγ-responsive tumors, and in vivo Matrigel vascularization assays revealed that while IFNγ-responsive and -unresponsive tumor cells induced anglogenesis equally well, IL-12 and its downstream mediator IFNγ, 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 IFNγ, inhibit tumor growth by inducing tumor cells to generate antiangiogenic activity.

UR - https://www.scopus.com/pages/publications/17344383269

UR - https://www.scopus.com/pages/publications/17344383269#tab=citedBy

U2 - 10.1016/S1074-7613(00)80585-3

DO - 10.1016/S1074-7613(00)80585-3

M3 - Article

C2 - 9697833

SN - 1074-7613

VL - 9

SP - 25

EP - 34

JO - Immunity

JF - Immunity

IS - 1

ER -