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Modulation of Plasminogen Activator Activity in Human Endometrial Adenocarcinoma Cells by Basic Fibroblast Growth Factor and Transforming Growth Factor ß¹

Chair of General Pathology, Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, via Valsabbina, 19, 25124 Brescia, Italy [M. P., J. A. M. M., M. R., G. R.], and Department of Cell Biology and Kaplan Cancer Center, New York University Medical Center, 550 First Avenue, New York, New York 10016 [D. M.]

Human endometrial adenocarcinoma HEC-1-A and HEC-1-B cells produce and secrete the urokinase-type plasminogen activator and trace amounts of the tissue-type plasminogen activator. The two clones, which originate from the same tumor, possess high affinity binding sites for basic fibroblast growth factor (bFGF) and they respond to the addition of human recombinant bFGF with an increase of the synthesis and secretion of urokinase-type and tissue-type plasminogen activators and with an increase in cell proliferation. Transforming growth factor ß, (TGFß), when added alone or 6 h before bFGF, induces an increase of plasminogen activator synthesis in both cell lines and stimulates the production of the endothelial cell-type plasminogen activator inhibitor in HEC-1-A cells, but not in HEC-1-B cells. Moreover, TGFß inhibits basal proliferation of both cell lines and suppresses the mitogenic activity of bFGF. We have previously demonstrated that HEC-1-A and HEC-1-B cells produce significant amounts of bFGF. On the basis of the well-established coordinate modulation of solid tumor growth and plasminogen activator production, our data suggest that bFGF may contribute, in an autocrine fashion, to the development of endometrial carcinomas. Moreover, endometrial tumor cells appear also to be a target for TGFß. Our results demonstrate also that significant qualitative and quantitative differences in the response to growth factors exist in clones derived from the same tumor, and support the view that the properties of in vivo tumors cannot be extrapolated from results obtained with a single isolate of tumor cells.

¹ This work was supported by a grant from the Associazione Italiana per la Ricerca sul Cancro to M. Presta, by grants from Ministero della Pubblica Istruzione (MPI, 40%, National Project of Experimental Oncology) and from CNR (Progetto Finalizzato Oncologia) to G. Ragnotti, and by grant n. 1811 from the Council for Tobacco Research-USA, Inc. to D. Moscatelli.

² To whom requests for reprints should be addressed.

Received 3/22/88. Revised 7/12/88. Accepted 7/29/88.

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