INFLUENCE OF SPATIAL CONFIGURATION OF CARCINOMA CELL-POPULATIONS ON THE EXPRESSION OF A TUMOR-ASSOCIATED GLYCOPROTEIN

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (2) , 833-840
Abstract
Monoclonal antibody B72.3 was generated using a membrane-enriched fraction of cells from a mammary carcinoma metastasis and has a high degree of selective reactivity for human breast and colon carcinoma vs. normal adult tissues. The reactive antigen was a high MW glycoprotein complex of approximately 220,000 to 400,000 and is termed tumor-associated glycoprotein T2 (TAG-72). A dichotomy in the expression of TAG-72 in carcinoma biopsy material vs. carcinoma cell lines is reported. While 44% (25 of 56) of human breast carcinoma and 80% (16 of 20) of colon carcinoma biopsies express TAG-72 as assayed by radioimmunoassay for immunohistochemistry, only 1 of 25 breast cancer cell lines [MCF-7 (1 variant)] and 1 of 18 colon cancer cell lines (LS-174T) express this antigen. TAG-72 expression in these 2 cell lines was a property of a low percentage of cells within each culture. Attempts to enhance TAG-72 expression in LS-174T cells by propagation on extracellular matrix proteins, such as collagen, laminin and fibronectin, or in serum-containing or serum-free, hormone-supplemented medium proved unsucessful. A pronounced increase in TAG-72 expression was observed, however, when the LS-174T cells were grown under culture conditions which promote 3-dimensional growth. LS-174T cells grown in spheroid or suspension cultures demonstrated a 2- to 7-fold increase in TAG-72 antigen expression, while those grown on agar plugs demonstrated a 10-fold increase. When the LS-174T cell line was injected into athymic mice to generate tumors, the level of TAG-72 antigen increased over 100-fod, to levels comparable to those seen in the metastatic tumor masses from patients. Spatial configuration of carcinoma cell populations influences the expression of a tumor-associated antigen and the subsequent surface binding of monoclonal antibody B72.3. The implications of these findings in the potential utility of monoclonal antibodies for the in vivo detection and destruction of carcinoma masses are discussed.