Re-assessment of acidic glycosphingolpids in small-cell-lung-cancer tissues and cell lines

The occurrence of tumor-associated glycosphingolipids (GSLs) has been documented in a variety of cancer tissues (Hakomori, 1984, 1985, 1989). In the case of small-cell lung cancer (SCLC), the monosialoganglioside IV2Fuc-II3NeuAc-Gg4Cer (Fuc-GM1; short notations of gangliosides are according to Svennerholm, 1963), first described from bovine liver (Wiegandt, 1973), was found to be a unique tumor-associated GSL (Nilsson et al., 1984). It is present in up to 90% of all SCLC cases as compared with 25% frequency in non-SCLC, and no occurrence in normal lung (Brezicka et al., 1989, 1992). Thus, Fuc-GM1 may represent a suitable target antigen for immunotherapy of SCLC, and successful experiments have been performed showing tumor-cell killing by monoclonal antibodies (MAbs) against Fuc-GM1, both in vitro and, in a mouse model, in vivo (Brezicka et al., 1991). However, an effective tumor vaccination in humans would require this antigen to be expressed by the primary tumor and also by all metastases. The co-expression of Fuc-GM1 has already been reported in primary tumors and in most but not all metastases of SCLC (Hanquing et al., 1986; Nilsson et al., 1986; Brezicka et al., 1989). In view of the significance this ganglioside may have for possible immunotherapeutical approaches to SCLC and of the difficulty in obtaining a sufficient number of samples for analysis, a re-assessment of Fuc-GM1 expression was made in SCLC primary tumors and their metastases, as well as in established SCLC cell lines. In addition, the possible presence of such gangliosides, that might help to explain the selective tetanus-toxin binding of SCLC cells (Critchley et al., 1986; Heymanns et al., 1989) was investigated. Finally, the typical occurrence of sulfatide in all SCLC tissues and cell lines could be established.