title: Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo.
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 alpha-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.
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: C
authors.initials: C
authors.lastname: Sgadari
authors.forename: A L
authors.initials: AL
authors.lastname: Angiolillo
authors.forename: B W
authors.initials: BW
authors.lastname: Cherney
authors.forename: S E
authors.initials: SE
authors.lastname: Pike
authors.forename: J M
authors.initials: JM
authors.lastname: Farber
authors.forename: L G
authors.initials: LG
authors.lastname: Koniaris
authors.forename: P
authors.initials: P
authors.lastname: Vanguri
authors.forename: P R
authors.initials: PR
authors.lastname: Burd
authors.forename: N
authors.initials: N
authors.lastname: Sheikh
authors.forename: G
authors.initials: G
authors.lastname: Gupta
authors.forename: J
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: G
authors.initials: G
authors.lastname: Tosato
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000473:pathology* / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology*; D017931:DNA Primers; D004854:Herpesvirus 4, Human; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D017931:DNA Primers; D011994:Recombinant Proteins