Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo

Cecilia Sgadari, Anne L. Angiolillo, Barry W. Cherney, Sandra E. Pike, Joshua M. Farber, Leonidas G. Koniaris, Padmavathy Vanguri, Parris R. Burd, Nasreen Sheikh, Ghanshyam Gupta, Julie Teruya-Feldstein, Giovanna Tosato

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194 Scopus citations

Abstract

Human Burkitt lymphoma cell lines give rise to progressively growing subcutaneous tumors in athymic mice. These tumors are induced to regress by inoculation of Epstein-Barr virus-immortalized normal human lymphocytes. In the present study, analysis of profiles of murine cytokine/chemokine gene expression in Burkitt tumor tissues excised from the nude mice showed that expression of the murine α-chemokine interferon-inducible protein-10 (IP- 10) was higher in the regressing than in the progressive Burkitt tumors. We tested the effects of IP-10 on Burkitt tumor growth in nude mice. Inoculation of established Burkitt tumors either with crude preparations of murine IP-10 or with purified human IP-10 caused visible tumor necrosis in a proportion of the animals, although no complete tumor regressions were observed. Constitutive expression of murine IP-10 in Burkitt cells reduced their ability to grow as subcutaneous tumors, and caused visible tumor necrosis in a proportion of the animals. Histologically, IP-10-treated and IP-10-expressing Burkitt tumors had widespread evidence of tumor tissue necrosis and of capillary damage, including intimal thickening and vascular thrombosis. Thus, IP-10 is an antitumor agent that promotes damage in established tumor vasculature and causes tissue necrosis in human Burkitt lymphomas established subcutaneously in athymic mice.

Original languageEnglish (US)
Pages (from-to)13791-13796
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number24
DOIs
StatePublished - Nov 26 1996
Externally publishedYes

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    Sgadari, C., Angiolillo, A. L., Cherney, B. W., Pike, S. E., Farber, J. M., Koniaris, L. G., Vanguri, P., Burd, P. R., Sheikh, N., Gupta, G., Teruya-Feldstein, J., & Tosato, G. (1996). Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo. Proceedings of the National Academy of Sciences of the United States of America, 93(24), 13791-13796. https://doi.org/10.1073/pnas.93.24.13791