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University of Colorado Cancer Center, Department of Biochemistry, Biophysics and Genetics [D. E. P., P. L. S., O. P.], and Department of Surgery [R. B. H., M. E. C., M. R. J.], University of Colorado Health Sciences Center, Denver, Colorado 80262
Cells of cloned lines of human squamous lung carcinomas elaborate large glycoproteins that are associated with their tumorigenic potential. Two groups of clones (called Lea-X-positive and Lea-X-negative) were studied that either do or do not express the Lea-X oligosaccharide associated with large glycoproteins and mucins secreted by these clones. Lea-X-positive cells elaborate a mucin gel complex associated with their apical surfaces, which appears as a mosaic of extracellular plates. Clones of this type are tumorigenic in nude rodents when injected s.c. or when introduced into the lungs via intrabronchial aerosol. By contrast, the Lea-X-negative clones do not form extracellular plates and are not tumorigenic in the lungs or subcutaneously. We demonstrate that the extracellular plates of Lea-X-positive cells exclude antibodies from interacting with the underlying squamous lung carcinoma cells and may therefore exert an immunoprotective effect. In support of this possibility it was found that: (a) There is a substantial inflammatory cell infiltrate associated with regressing nodules of Lea-X-negative cells in nude rodent lung and subcutaneous nodules, while there is no observable infiltration associated with progressing Lea-X-positive tumors. (b) In the brain (an immunoprivileged site) tumors develop and progress when either Lea-X-negative or -positive cells are introduced.
1 Supported by Grant BC-685 from the American Cancer Society (D. E. P.) and by NIH National Cooperative Drug Discovery Group Grant CA46088 (M. R. J.).
2 Present address: Samuel Lunenfeld Research Institute, Division of Thoracic Surgery, Mt. Sinai Hospital, Room 643, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5.
3 Present address: Cardiothoracic Centre, Thomas Drive, Liverpool, England L14 3LB.
4 To whom requests for reprints should be addressed, at Department of Biochemistry, Biophysics and Genetics, Box B188, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262.
Received 10/22/91. Accepted 3/10/92.
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