Monoclonal antibodies (MAb; DMAb,
monoclonal antibodies derived at Duke Medical Center) directed against the oncofetally expressed lactotetraosyl
gangliosides 3'-isoLM1 (IV3NeuAc-LcOse4Cer) and 3',6'-isoLD1 (IV3NeuAc,III6NeuAc-LcOse4Cer) were produced and their reactivity spectra compared to that of the alpha-3'-isoLM1 MAb SL-50. The
IgM MAb SL-50 defines the
epitope NeuAc (or NeuGc)alpha 2-3Gal beta 1-3GlcNAc, the terminal sequence of both
gangliosides. SL-50 requires an unsubstituted GlcNAc residue;
IgM DMAb-14 will accept the alpha 2-6 linked
sialic acid to GlcNAc found in 3',6'-isoLD1. Immunohistochemical localization of 3'-isoLM1 was performed on 31 biopsy specimens of human
gliomas; 15 (48%) expressed 3'-isoLM1 as defined by binding of MAb SL-50. Staining of small anaplastic cells, giant cells, and the glial component of
gliosarcomas was observed. Neoplastic gemistocytes, when present, showed particularly intense staining. The 3'-isoLM1 and 3',6'-isoLD1 distribution in cultured cell lines and derived xenografts of primary
tumors of the human central nervous system and of embryonal or
neuroectodermal tumor derivation was determined. Six of 29 cell lines expressed 3'-isoLM1: 2/16
gliomas, 3/3
teratomas, 1/1 pancreatic
adenocarcinoma. No cell line expressed detectable 3',6'-isoLD1 by immunostain analysis of
ganglioside extracts. The 3'-iso-LM1-positive cell lines expressed it in xenograft form; in five xenografts, the corresponding cell lines of which were 3'-isoLM1-negative, it was a proportion of the monosialoganglioside fraction. 3',6'-isoLD1 was detected in two xenografts, D-54 MG (
glioma) and PA-1 (
teratoma). The demonstration of 3'-isoLM1 in
gliomas in in vivo forms and the relatively infrequent expression by derived cultured cells suggest that
ganglioside expression is modified by environmental forces. Expression of 3'-isoLM1 and 3',6'-isoLD1 in fetal and neonatal brain, in intense reactive
astrocytosis such as
polyunsaturated fatty acid lipidosis, and in primary
neoplasms of the central nervous system suggests their role in cell-cell attachment during development, migration, and neoplastic transformation.