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Lactotetraose Series Ganglioside 3',6'-isoL_D1 in Tumors of Central Nervous and Other Systems in Vitro and in Vivo¹

Departments of Pathology [C. J. W., D. C. L., R. E. M., G. N. F., H. S. F., D. D. B.] and Pediatrics [H. S. F.], and Preuss Laboratory for Brain Tumor Research [H. S. F., D. D. B.], Duke University Medical Center, Durham, North Carolina 27710; and Department of Psychiatry and Neurochemistry, University of Göteborg, Göteborg, Sweden [P. F., L. S.]

Two monoclonal antibodies, DMAb-21 and DMAb-22, directed against the lactotetraose series ganglioside-associated epitope IV³NeuAc,III⁶-NeuAcLcOse₄Cer (3',6'-isoL_D1), were found to define the minimum binding epitope NeuAc(or NeuGc)2-3Galß1-3(NeuAc or NeuGc)2-6GlcNAc. The distribution of 3',6'-isoL_D1 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. Only 4 of 26 cell lines, 3 teratomas and 1 pancreatic adenocarcinoma, expressed detectable 3',6'-isoL_D1 when cultured in vitro; none of 14 tested glioma lines, including 2 that expressed the monosialo-precursor IV³NeuAcLcOse₄Cer in vitro, expressed detectable levels. Expression of 3',6'-isoL_D1 was more frequent when neoplastic cells were grown in xenograft form in athymic mice; 4 of 10 glioma and 2 of 2 teratoma xenograft ganglioside extracts were positive for 3',6'-isoL_D1. The absence of 3',6'-isoL_D1 in cultured tumor cells of the central nervous system and its proportional increased presence in tumor cells of the same origin grown in vivo further supports previous studies suggesting that ganglioside expression may be modified by environmental forces. The expression of lacto series gangliosides both in vitro and in vivo by teratoma and pancreatic adenocarcinoma cells, as opposed to only in vivo expression by glioma cells, suggests that tissue-specific forces may also exist. Immunohistochemical localization of 3',6'-isoL_D1 in frozen sections of primary central nervous system neoplasms including those of glial and nonglial origin was performed; 20 of 30 (67%) of glial tumors were positive. Among nonglial tumors, 21 of 34 (62%) of epithelial cancers were reactive with anti-3',6'-isoL_D1 monoclonal antibodies; notably negative were carcinomas of the ovary and lung carcinomas of all subtypes. Lymphomas and infiltrative lymphocytes were uniformly negative. The restriction of 3',6'-isoL_D1 expression within the human central nervous system to periods of fetalneonatal astroglial proliferation, to intense reactive astrocytosis, and to primary neoplasms, and the production of specific monoclonal antibodies to this epitope provide a specific complex for immunolocalization and, eventually, immunotherapy.

¹ Supported by NIH Grants CA 11898, NS 20023, T32-NS 07304, CA 56115, and CA 44640; by the Swedish Medical Research Council (Project 03X-09909-01); and by the National Swedish Board for Technical Development (Project 84-4667P).

² Present address: Division of Hematology/Oncology, Arkansas Children's Hospital, 800 Marshall Street, Little Rock, AR 72202-3591.

³ To whom requests for reprints should be addressed, at Box 3156, Department of Radiology, Duke University Medical Center, Durham, NC 27710.

Received 8/12/92. Accepted 10/20/92.

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