Enhanced metastases of a mouse carcinoma after in vitro treatment with murine interferon gamma

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Abstract
We have studied the influence of inter ferons (IFNs) on the metastatic potential of mouse colon adenocarcinoma, COLON 26, cells. Pre-treatment of the cells in vitro for 24 hr with recombinant murine IFN-γ (rMuIFN-γ) significantly in-creased the number of lung tumour nodules when cells were injected i.v. into immunocompetent BALB/c mice and BALB/ c nude mice. However when MulFN-γ-pre-treated cells were injected into beige (NK-deficient) nude mice or anti-asialoGM I (as GMI)-serum-treated BALB/c mice (NK-depleted) no enhancement of metastatic potential was seen. Pre-treatment of COLON 26 cells with recombinant human IFN-α A/D (Bgl I), an IFN with equal activity on human and mouse cells, did net significantly enhance their subsequent metastases in immunocompetent or immunodeficient mice. In fact, there was a small but significant decrease in the number of tumour nodules in the lungs of beige nude and asGM I -treated mice. The e effects of rMuIFN-γ on COLON 26 cells did not appear to be related to an alteration in MHC expression. COLON 26 eel Is constitutively express H-2D and H-2K antigens and both IFNs had equal enhancing (approx. 2-fold) activity on the expression of these antigens at the doses used in this experiment (103 U/ml). We conclude that pre-treatment with rMuIFN-γ renders COLON 26 cells resistant to in vivo NK-cell lysis via a mechanism that does not involve changes in MHC expression.