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Fibronectin and Glial Fibrillary Acidic Protein Expression in Normal Human Brain and Anaplastic Human Gliomas¹

Department of Pathology, Medicine, and Surgery, Duke University Medical Center, Durham, North Carolina 27710, and La Jolla Cancer Research Foundation, La Jolla, California 92037

The expression of fibronectin (FN), an extracellular matrix glycoprotein with adhesive and opsonic properties, was examined in normal and neoplastic human central nervous system tissues. In both normal adult and fetal brain, FN expression, as detected by immunohistochemistry, was restricted to the vasculature. Neurons and glia did not stain. FN expression in nine of 10 gliomas examined was qualitatively similar to that in normal fetal and adult brain in that it was confined to the blood vessels. Nevertheless, in one case, there was interstitial expression of FN. Four tumors exhibited varying degrees of fibroblastic overgrowth in which cells containing FN were detected. Frozen sections of eight athymic mouse-borne anaplastic human gliomas were stained simultaneously by a double-label fluorescein-rhodamine fluorescence technique for both FN and glial fibrillary acidic protein (GFAP), a glial and glioma marker. Seven of eight tumors expressed FN, seven of eight expressed GFAP, and six of eight expressed both. FN was detected as fine fibrils and specks between cells while GFAP presented as a homogeneous intracellular fluorescence. In many areas of the tumors, groups of cells expressed both FN and GFAP. Eleven human glioma-derived cell lines were examined for both FN and GFAP expression. In two cell lines, there were cells which contained both GFAP and FN simultaneously. Athymic mouse-borne tumors were developed by the injection of an FN-producing glioma-derived cell line into athymic mice. Human FN plasma levels were monitored, and some tumors larger than 1.0 g produced FN which was detectable in the plasma, thereby demonstrating that tumor-produced FN can be shed from human glioma-derived cells in sufficient amounts to be detectable in the bloodstream. These data show that FN expression in anaplastic human gliomas is seen with the greatest frequency in athymic mouse-borne tumors; GFAP-positive cultured cells are also capable of FN expression. The original tumors rarely express detectable amounts of FN. The biological basis for this heterogeneity of FN expression rests in the nature of the individual tissue studied, its cellular environment (i.e., in vivo or in vitro), and its status with regard to neoplasia.

¹ This investigation was supported in part by National Cancer Institute Grants CA-11898, CA-22790, and CA-28896, National Institute of Neurological and Communicative Disorders and Stroke Grant 1-R23-NS-16974, American Cancer Society Grant CH191, and the Roy Alexander Brain Tumor Research Fund.

² To whom requests for reprints should be addressed.

Received 8/13/81. Accepted 10/17/81.

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