Conversion of human fibroblasts to tissue macrophages by the Snyder-Theilen feline sarcoma virus (ST:FeSV): tumoricidal potential in monolayers and in agar suspensions.
In earlier studies [1-3], we have demonstrated the conversion of human fibroblasts (HF) to tissue macrophages (TM) by the Snyder-Theilen feline sarcoma virus (ST:(FeSV)). The purpose of the present study is to determine the cytolytic potential of ST:FeSV(FeLV)-induced TM against tumorigenic target cells under defined conditions in vitro. The results show that ST:FeSV-induced TM, but not mock-infected HF, produced significant lysis of human colon adenocarcinoma cells (LS-180) after a 3-day preincubation period, followed by a 4-day coincubation period at an effector to target cell ratio of 5:1. The presence of IFN-gamma, or lipopolysaccharides (LPS), and especially of M-CSF, during the coincubation period generally yielded optimal lysis of the tumor cells. Addition of LS-180 specific antibody (NRCO-4) substantially increased the cytolytic potential of TM. Significantly, coincubation of TM with LS-180 tumor cells in an agar medium, where no direct contact between cells occurs, resulted in the inhibition of tumor cell proliferation. Addition of LPS has further accentuated this inhibition. The results indicate that ST:FeSV-induced macrophages are potent oncocytolytic agents of LS-180 tumor cells in the absence and in the presence of direct contact between effector and target cells.
Kopelovich
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Laboratory of Cancer Genetics and Cancer Prevention, Départment of Veterans Affairs, Bay Pines, Florida.
D000230:Adenocarcinoma / Q000276:immunology*; D002472:Cell Transformation, Viral; D003110:Colonic Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D005253:Sarcoma Viruses, Feline / Q000502:physiology*; D014407:Tumor Cells, Cultured