Evidence for the expression of human tumor-specific antigens associated with beta2-microglobulin in human cancer and in some colon adenomas and benign breast lesions.

Abstract

The blocking tube leukocyte adherence inhibition (LAI) assay was used to monitor the purification of human tumorspecific antigens (TSA's) from colon and breast cancer and malignant melanoma. The tumor antigens were specific for the organ from which the cancer arose and the histopathology of the cells of origin. Immunochemical studies revealed that TSA could be water solubilized from cancer cell membranes by limited papain digestion, and on Sephadex G-150 chromatography the majority of the TSA eluted in the molecular-weight range of 70,000 to 150,000. Affinity chromatography with anti-human β2-microglobulin (β2m) antiserum indicated that the TSA's, like HLA molecules, contain a β2m subunit. The specificity of binding of the TSA to the anti-β2m immunoadsorbent affinity column and the immunologically specific abrogation of LAI activity were shown. Some patients with either colon adenomas or benign breast disease showed LAI activity to phosphate-buffered saline extracts of colon and breast cancer, respectively, but did not react to extracts of normal colon mucosa or breast tissue. Moreover, the LAI-reactive leukocytes were blocked by the papain-soluble TSA's from colon and breast cancer, respectively, purified by anti-β2m affinity chromatography. The present studies suggest that some “benign” lesions express TSA's before the appearance of morphological evidence of cancer. It is not known, however, if the acquisition of a cell surface TSA is an irreversible step toward unrestrained growth and metastasis. In addition, the present studies indicate that the putative TSA's of cancers of different organs are similar in subunit structure, size, and genetic linkage and have some unexplained relationship to organ definition.