LEUKEMIA INHIBITORY FACTOR DERIVED FROM RAT COLON-CARCINOMA CELLS INCREASES HOST SUSCEPTIBILITY TO TUMOR-GROWTH

We have tested Leukaemia Inhibitory Factor (LIF) production by 12 rat colon tumour clones isolated from a single cell line that display vari ous degrees of tumorigenicity A highly significant relationship was Bo und between levels of soluble LIF produced by the clones and their in vivo tumorigenicity, Such results suggested a role for LIF as a tumour facilitating agent, To test this hypothesis, the highly tumorigenic a nd LIF producing PROb clone was transfected with the LIF cDNA in antis ense orientation in order to decrease LIF production, Conversely, REGb , a low LIF producer that is rejected by syngeneic animals, as well as nude mice, was transfected,vith the LIF cDNA to increase its producti on, PROb cells transfected with antisense cDNA were shown to have decr eased LIF production along with decreased tumorigenicity, LIF-transfec ted REGb cells expressing high LIF levels still regressed in syngeneic rats, but could form progressive tumours in nude mice, We did not det ect LIF receptors on PROb or REGb cells and their in vitro proliferati on was not modified by the addition of exogenous LIE Therefore, LIF wa s not an autocrine growth regulator for PROb and REGb cells, Instead, LIF appears to facilitate in vivo tumour growth, without being an immu nosuppressive factor sufficient on its own to allow growth of immunoge nic cells in fully immunocompetent hosts.