Alteration of the metastatic potential of line 1 lung carcinoma cells: opposite effects of class I antigen induction by interferons versus DMSO or gene transfection.
Class I antigens are necessary for the recognition of tumor cells by cytotoxic T lymphocytes (CTL). The line 1 lung carcinoma is a spontaneous murine tumor deficient in class I antigen expression. Consistent with this, line 1 cells are highly metastatic in vivo. We investigated whether increasing class I antigen expression on line 1 cells could alter the metastatic potential of these tumor cells using an in vivo lung metastasis model. We used three methods to induce class I antigen expression on line 1 cells: gene transfection, treatment with dimethyl sulfoxide (DMSO), or treatment with interferon (IFN)-beta or -gamma. We found that line 1 cells expressing a transfected class I gene were significantly less metastatic than parental line 1 cells. DMSO-treated line 1 cells also formed significantly fewer metastases than parental line 1 cells. These results indicate that increased class I antigen expression decreases the metastatic potential of line 1 cells in vivo. However, we did not observe a significant decrease in the number of lung metastases in mice receiving line 1 cells treated with IFN-beta or -gamma, despite high levels of class I antigen expression. Thus, increasing class I antigen expression with IFN has an opposite effect on metastasis from class I antigen expression induced by transfection or DMSO. These results show that the method used to increase class I antigen expression is critical in terms of the in vivo effect observed. To investigate a possible mechanism for the differences observed in vivo between these class I expressing cells, we tested whether IFN alters or blocks susceptibility of line 1 cells to immune effector cells. We found IFN treatment increased the ability of line 1 cells to be recognized by CTL but concomitantly decreased the susceptibility of line 1 cells to NK cell lysis by a non-class I antigen-related mechanism. In contrast, transfected or DMSO-treated line 1 cells which were less metastatic in vivo were susceptible to both CTL and NK-mediated lysis. Taken together, these results suggest that immune intervention against metastasizing line 1 cells may involve NK cells and CTL.
Cancer Center Immunology Unit, University of Rochester School of Medicine and Dentistry, New York 14642.
K M
KM
Cerosaletti
T M
TM
Blieden
L W
LW
Harwell
K M
KM
Welsh
J G
JG
Frelinger
E M
EM
Lord
D000818:Animals; D002277:Carcinoma / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007372:Interferons / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis; D014162:Transfection; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D007372:Interferons; D004121:Dimethyl Sulfoxide