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Human Mesothelioma Cells Produce Factors That Stimulate the Production of Hyaluronan by Mesothelial Cells and Fibroblasts¹

Department of Medical and Physiological Chemistry, Box 575, Biomedical Center, S-751 23 Uppsala, Sweden [T. A., T. C. L., P H.], and Department of Immunology, Erasmus University, P. O. Box 1738, 3000 DR Rotterdam, the Netherlands [M. A. V.]

² To whom requests for reprints should be addressed.

The hyaluronan production by three human malignant mesothelioma cell lines and nine primary human mesothelial cell types was determined. The mesothelioma cell lines produced only minute amounts of hyaluronan (less than 0.1 µg/10⁶ cells/48 h) whereas mesothelial cells synthesized large quantities of hyaluronan (10–72 µg/10⁶ cells/48 h). Conditioned media from the mesothelioma cell lines were investigated for their ability to stimulate hyaluronan production by fibroblasts and mesothelial cells in vitro, and in all cases stimulatory effects were found. The factor(s) in the conditioned medium of the mesothelioma cell line Mero-25 that were responsible for hyaluronan stimulation were heat stable and partially trypsin resistant. The stimulatory activity was partially inhibited by an antiserum against platelet-derived growth factor and basic fibroblast growth factor. Our data suggest that the increased hyaluronan synthesis seen in patients with mesothelioma is due to the release of factors from mesothelioma cells that stimulate other cells to produce hyaluronan.

¹ This project was supported in part by grants from the Swedish Medical Research Council (O3X-4), the Royal Swedish Academy of Sciences, and Gustav V:s 80 åars fond.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 4/30/92. Accepted 11/ 4/92.

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