Differential responsiveness of cloned mammary carcinoma cell populations to the human recombinant leukocyte interferon enhancement of tumor antigen expression.

Abstract

We have previously shown that a recombinant human leukocyte interferon (IFN-alpha A)5 can mediate an increase in cell surface tumor antigen expression in human carcinoma cells but not normal cells (Greiner et al., 1984). Such a biological response modifier may prove useful in circumventing the problem of antigenic heterogeneity and could increase the effectiveness of monoclonal antibodies (MAbs) for detection and/or therapy of human carcinoma lesions. These studies also revealed that, within populations of human carcinoma cells, there exist subpopulations which are unresponsive to the antigen-enhancing properties of IFN-alpha A. Utilizing cloned cell populations from the MCF-7 human breast carcinoma cell line, we now report the differential responsiveness to the tumor antigen enhancing and antiproliferative actions of IFN-alpha A. Binding of MAb B72.3 to the 220-400 kd tumor antigen, TAG-72, is increased by IFN-alpha A treatment on the surface of the parental MCF-7 cell line and 2 cloned cell populations. A third MCF-7 clone does not express this antigen either before or after IFN-alpha A treatment, but does express a 90 kd tumor antigen and carcinoembryonic antigen which bind MAbs B6.2 and B1.1, respectively. The level of expression of these 2 surface tumor antigens remained unchanged upon interferon treatment. The growth of the parental MCF-7 cells and the 3 cloned cell lines was, however, inhibited by IFN-alpha A. These cell lines also exhibited approximately the same number of interferon receptors with similar binding affinities for IFN-alpha A. The results demonstrate a dissociation of two biological actions of IFN-alpha A-antiproliferative activity and enhancement of tumor antigen expression within a cloned human carcinoma cell line. Our studies also indicate that the differential response of cloned MCF-7 cells to tumor antigen modulation by interferon involves alterations in the transduction of signals occurring distal to receptor occupancy within the biochemical pathways responsible for the actions of this biological response modifier. In addition, the clonal cell lines we have isolated which differ in their responsiveness to interferon should prove valuable in analyzing the molecular basis of interferon actions and may provide insights into the mechanism by which this compound confers its antitumor activity.