Glycoconjugates in nervous tissue and small cell lung cancer share immunologically cross-reactive carbohydrate determinants

Abstract

Small cell lung cancer (SCLC) is a bronchogenic carcinoma of neuroectodermal origin that expresses a variety of nervous system markers characteristic of neuroendocrine cells. In addition, SCLC cell lines and biopsies have been shown immunocytochemically to express an antigen recognized by HNK-1, a mouse monoclonal antibody which recognizes a surface antigen on natural killer cells and on the myelin-associated glycoprotein (MAG) and other nervous system glycoconjugates. Immunoblot data are presented which identify 2 groups of HNK-1 reactive plasma membrane glycoproteins with Mrs of about 80 000 and 130 000, respectively, from several SCLC cell lines. Using antibodies to MAG carbohydrate and protein determinants as probes, it is shown that the SCLC glycoproteins reacting with HNK-1 do not appear to share structural similarity with MAG apart from carbohydrate determinants. Using similar techniques with a panel of polyclonal antibodies, data are shown indicating that there is no cross-reactivity of SCLC proteins with other myelin proteins including P0, P1, P2, proteolipid protein and myelin basic protein. A possible role of the carbohydrate antigen in mediating nervous system disease associated with SCLC is suggested. Small cell lung cancer (SCLC) is a bronchogenic carcinoma of neuroectodermal origin that expresses a variety of nervous system markers characteristic of neuroendocrine cells. In addition, SCLC cell lines and biopsies have been shown immunocytochemically to express an antigen recognized by HNK-1, a mouse monoclonal antibody which recognizes a surface antigen on natural killer cells and on the myelin-associated glycoprotein (MAG) and other nervous system glycoconjugates. Immunoblot data are presented which identify 2 groups of HNK-1 reactive plasma membrane glycoproteins with Mrs of about 80 000 and 130 000, respectively, from several SCLC cell lines. Using antibodies to MAG carbohydrate and protein determinants as probes, it is shown that the SCLC glycoproteins reacting with HNK-1 do not appear to share structural similarity with MAG apart from carbohydrate determinants. Using similar techniques with a panel of polyclonal antibodies, data are shown indicating that there is no cross-reactivity of SCLC proteins with other myelin proteins including P0, P1, P2, proteolipid protein and myelin basic protein. A possible role of the carbohydrate antigen in mediating nervous system disease associated with SCLC is suggested.