Modulation and biological effects of Ly-6.2 expression on EL4 tumour cells

Abstract

Summary EL4 tumour cells maintained in culture were separated by FACS analysis to Ly-6.2 negative and Ly-6.2 positive subsets. The Ly-6.2 negative subset gained expression of this determinant on repeated in vivo passage in C57BL/6 mice. Both subsets injected intraperitoneally or intramuscularly in syngeneic mice induced identical changes in lymphocyte profiles. There was generalised lymphocytolysis in both T-and B-cell compartments. The Lyt-l +, 2-T-lymphocytes were more susceptible to cytolysis causing an alteration of the proportional representation of the Lyt-2+ subset from 30% of splenic T-cells Tumour cell populations are heterogeneous with respect to a variety of properties that influence their growth and survival in the host (Poste & Fidler, 1980;Nicholson, 1984). Development of heterogeneity is thought to be part of the tumorigenic process causing the progression of primary tumours from the benign to the malignant state (Harris et al., 1982;Fidler & Hart, 1982). This may involve the selection of stable subpopulations of cells in the original tumour which possess intrinsic properties that promote dissemination; it may also reflect the acquisition of such properties due to genetic alterations that may arise under the influence of selective pressures of the host response (Layton & Franks, 1984;Bernstein & Weinberg, 1985).Comparative examinations of metastatic variants and parental tumour lines have centred on the study of cell surface compositions of neoplastic cell lines. Quantitative differences in terminal cell surface carbohydrates (Fogl et al., 1983), altered cell surface protein composition after enzyme treatment (Sargent et al., 1983) and differences in glycoprotein expression (Altevogt et al., 1982) have all been shown to contribute to the metastatic capacity of different tumour cell lines. The most notable finding to date is an inverse correlation between metastatic potential and the expression of major histocompatibility complex (MHC) molecules (Wallich et al., 1985;Hui et al., 1984;Albino et al., 1981;Natali et al., 1983).In this study we demonstrate that in the EL4 murine Tcell leukaemia model there is a direct relationship between expression of the lymphocyte differentiation antigen Ly-6.2 and dissemination of the tumour cells to the spleen and lymph nodes from an intramuscular site. EL4 tumour cells maintained in culture are heterogeneous with respect to Ly-6.2 expression. Tumour cells selected by fluorescence activated cell sorter (FACS) analysis on the basis of lack of expression of Ly-6.2, gained this determinant on in vivo passage while parallel in vitro cultures remained negative. To determine the biological effects of Ly-6.2 expression on EL4 tumour cells, Ly-6.2-and Ly-6.2+ tumour cells were injected into syngeneic C57BL/6 mice and their effects on lymphocyte profiles and capacity to metastasize into the lymphoid organs examined. as a second step reagent. Monoclonal antibodies against Thy-I and Lyt-2 were derived from hybridoma clones 53-2.1 and 53-6.7 respectively (Ledbetter & Her...