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Correlation of Chondroitin Sulfate Proteoglycan Expression on Proliferating Brain Capillary Endothelial Cells with the Malignant Phenotype of Astroglial Cells¹

Research Institute of Scripps Clinic [M. S., F. G. K., R. C. S., T. A. W., R. A. R.], La Jolla, California 92037, and University of California, San Diego Medical Center [C. L. G.], San Diego, California 92103

Human gliobastomas (five of five), the most malignant astroglial-derived tumors, specifically express a chondroitin sulfate proteglycan that is recognized by monoclonal antibody 9.2.27 and localized to the glioma cell surface, proliferating endothelial cells, and the perivascular extracellular matrix within the tumor bed. In contrast, the expression of this proteoglycan in normal adult neocortex and white matter is limited to the smooth muscle of small arteries, while normal glia, endothelial cells, and endothelial cell basement membranes are nonreactive. Moreover, two anaplastic astrocytomas, representing medium-grade astroglial-derived tumors, fail to react with monoclonal antibody 9.2.27. In culture, glioblastoma and capillary brain endothelial cells specifically synthesize a 250-kDa core protein and a high-molecular-mass chondroitin sulfate proteoglycan, recognized by monoclonal antibody 9.2.27. These data suggest a correlation between the expression of this chondroitin sulfate proteoglycan on proliferating brain capillary endothelial cells and the malignant phenotype of astroglial cells. The prominent perivascular localization of chondroitin sulfate proteoglycan makes it a marker for both proliferating brain capillary endothelial cells and the most malignant transformed astroglial cells, thus providing an ideal target for the immunotherapy of glioblastoma.

¹ Supported in part by the Preuss Foundation for Brain Tumor Research and by NIH Grant CA42508. This is the Research Institute of Scripps Clinic Manuscript 6458IMM.

² Recipient of a fellowship of the Deutsche Forschungsgemeinschaft, Federal Republic of Germany.

³ To whom requests for reprints should be addressed, at Research Institute of Scripps Clinic, Dept. of Immunology, IMM13, 10666 N. Torrey Pines Road, La Jolla, Ca 92037.

⁴ Supported by PSA#5K12AG00353.

Received 3/14/91. Accepted 7/ 2/91.

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