Tumor formation by a murine macrophage cell line immortalized in vitro by v-raf and v-myc oncogenes

Abstract

Murine bone marrow cells immortalized in vitro by the J2 recombinant retrovirus bearing the v-raf and v-myc oncogenes have the functional and phenotypic characteristics of macrophages. The present study was designed to determine whether these cells are tumorigenic in athymic or euthymic mice. One cloned cell line (GG2EE), that had been previously derived and characterized was used for this purpose. The results demonstrated that GG2EE cells were tumorigenic in allogeneic athymic BALB/c mice at doses of 1×10⁴ to 1×10⁷ cells per mouse regardless of the route administration. All mice utlimately died of progressive tumor growth. Conversely, the GG2EE cells were nontumorigenic or transiently tumorigenic in syngeneic euthymic C3H/HeJ mice. Further studies in BALB/c athymic mice demonstrated that the GG2EE cells were directly tumorigenic since ascites tumors (GG2EE-V) that developed expressed the H-2^k surface phenotype of the injected GG2EE cells, excluding the possibility that the J2 virus constitutively produced by GG2EE cells caused in vivo transformation and therefore tumors of host cell origin. The in vivo passaged cells continued to express the M1/69, MAC-1, MAC-2, F4/80, Fc receptor and Ly5.1 antigens characterically expressed on the parental line. Biological properties including interferon-γ-induced Ia expression, phagocytosis, and activation for cytotoxicity were also retained following in vivo passage. These results demonstrated that J2 virus-immortalized GG2EE cells were directly tumorigenic in athymic mice in vivo and that the macrophage phenotype was maintained in these neoplastic cells. These observations suggest that this tumor model may be valuable for the study of macrophage function as well as therapeutic approaches to oncogen-expressing retrovirus-induced tumors.