Differentiation of human fibroblasts to tissue macrophages by the Snyder-Theilen feline sarcoma virus (ST:FeSV)

Abstract

We have previously reported the conversion of human fibroblasts (HF) to tissue macrophages (TM) by transduction with the Snyder-Theilen feline sarcoma virus [ST:FeSV(FeLV)]. Here, we have demonstrated macrophage mediated tumor cytotoxicity (MTC) of human teratocarcinoma cells (NTERA-2) by ST:FeSV-induced TM. Inclusion of the NTERA-2 specific antibody (SSEA-4), substantially increased antibody-dependent cellular cytotoxicity (ADCC) of the tumor cells by ST:FeSV-induced TM. Tumor cell lysis by ST:FeSV-induced TM through either MTC or ADCC was especially effective at low serum concentrations (1%). The presence of cytokines during co-incubation, M-CSF in particular, enhanced the lysis of NTERA-2 cells by ST:FeSV-induced TM. Whereas pretreatment of the NTEBA-2 cells with all-trans retinoic acid (AtRA) enhanced MTC-induced lysis, it abrogated ADCC-induced lysis of the tumor cells by ST:FeSV-induced TM. Significantly, the co-incubation of NTERA-2 cells with ST:FeSV-induced TM in agar, resulted in a considerable stimulation of growth of untreated and TPA-pretreated NTERA-2 cells. In contrast, the growth of AtRA-pretreated NTERA-2 cells in agar was completely inhibited by ST:FeSV-induced TM. These results indicate that ST:FeSV-induced TM can produce potent growth-modulating cytokines, and that AtRA can modify their antitumor activity in monolayer cultures and in agar. The effects by AtRA, serum, and growth conditions (whether monolayers or agar) point to several levels of complexity regarding the interaction of tissue macrophages with tumor cells.