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Expression and Cellular Localization of Messenger RNA for Plasminogen Activator Inhibitor Type 1 in Human Astrocytomas in Vivo¹

Departments of Neurosurgery [M. Y., R. S., S. M., J. S. R.], Pathology [J. M. B.], Tumor Biology [G. L. N.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; Research Institute of Scripps Clinic, La Jolla, California 92037 [D. J. L.]; Connective Tissue Research, University of Nebraska Medical Center, Omaha, Nebraska, 68198 [V. H. R.]; and Department of Neurosurgery, Fukuoka University School of Medicine, Fukuoka, 814-01, Japan [K. O., M. T.]

We investigated the expression and cellular localization of plasminogen activator inhibitor type 1 (PAI-1) in human astrocytoma in vivo. Northern blot and densitometric quantitation of PAI-1 mRNA indicated that PAI-1 transcripts were significantly higher in human malignant astrocytomas and especially in glioblastomas than in low-grade gliomas and normal brain tissues in vivo. Using in situ hybridization with paraffin-embedded surgical specimens of human gliomas and normal brain tissues, PAI-1 mRNA was abundantly expressed in glioblastomas. PAI-1 mRNA was localized mainly in tumor cells and endothelial cells. The distribution of PAI-1 mRNA expression was particularly abundant around areas of vascular proliferation and in remnant tumor cells surrounding necrotic foci. PAI-1 mRNA was also expressed in both the tumor and endothelial cells of anaplastic astrocytomas, whereas it was not expressed or only weakly expressed in low-grade astrocytomas or normal brain tissues. These results suggest that high expression of PAI-1 is associated with the malignant progression of astrocytic tumors and that excessive PAI-1 expression might be associated with intratumoral necrosis in glioblastomas.

¹ Support for these studies was provided, in part, by Physicians Referral Service funds of The University of Texas M. D. Anderson Cancer Center, the Wendy Will Case Foundation, National Cancer Institute Grants CA 56792 (to J. S. R.) and CA 44352, and a grant from the National Foundation for Cancer Research, Inc. (to G. L. N.).

² To whom requests for reprints should be addressed, at Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Box 064, 1515 Holcombe Blvd., Houston, TX 77030.

Received 4/ 6/94. Accepted 5/19/94.

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