Carcinoma-associated 38-kD membrane glycoprotein MH 99/KS 1 4 is related to proliferation and age of transformed epithelial cell lines

Abstract

A 38-kD cell-surface glycoprotein (MH 99, KS 1 4) appears strongly elevated in epithelial malignancies, although it also occurs in a few immature, germ-cell phenotypic tissues in human epidermis. In this study, the expression and synthesis characteristics of the MH 99 antigen were examined in several transformed epithelial cell lines. Marked increase of MH 99 (by 100-200%) was found in highly proliferative cell populations, as demonstrated by radioimmunoprecipitation, fluorescence-activated cell sorter analysis, and proliferation experiments in cultures of spontaneously immortalized keratinocytes (HaCaT) squamous cell carcinoma lines (SCL 1 and SCL 2), and SV-40 transformed keratinocytes (130, 425, and HaSV). The relation of the MH 99 antigen to cell proliferation was underscored by a 70-75% decrease of synthesis in nonproliferating HaCaT cells treated with mitomycin C. Blocking of two distinct epitopes of the molecule with two different monoclonal antibodies (MH 99 and MM 104) decreased cell proliferation by approximately 25% (F = 519.6; df = 1,145; p < 0.0001), as compared to untreated cells and to cells treated with unrelated antibodies (BT 15 and J 143). Analysis of MH 99 synthesis in aging transformed keratinocytes cultured without passage revealed downregulation by approximately 50-60% after 60 d, indicating inverse correlation of the MH 99 antigen with increasing cell age. It seems, therefore, that the MH 99 antigen is directly correlated with cell proliferation and inversely correlated with increasing age of transformed epithelial cells, possibly playing an active role in the process of cell proliferation. © 1994.