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Characterization of Platelet-derived Growth Factor and Platelet-derived Growth Factor Receptor Expression in Asbestos-induced Rat Mesothelioma

Chemical Industry Institute of Toxicology [C. W., E. B., W. S., J. E.] and National Institute of Environmental Health Sciences [J. B.], Research Triangle Park, North Carolina 27709, and Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 [C. J. M.]

Although altered expression of platelet-derived growth factor (PDGF) is a hallmark of human mesothelioma, expression of PDGF receptors has not been characterized in this cell type. In addition, the expression of this growth factor and its cognate receptor in rodent mesothelioma has not been investigated. In this study, examination of transformed mesothelial cells derived from asbestos-induced rat mesotheliomas revealed that these cells expressed high affinity PDGF receptors (K_d = 0.5 nM) and receptor number was 1.6 x 10⁵/cell. Western analysis using antibodies specific for either the -type or ß-type PDGF receptor and Northern analysis using probes specific for - and ß-type receptor RNA transcripts indicated that these cells expressed ß-type PDGF receptors but that -type receptors could not be detected. However, when the mesothelioma-derived cells were examined for the expression of PDGF, no expression of this growth factor could be detected. The transformed cells expressed no detectable A- or B-chain PDGF RNA transcripts; and using a competitive enzyme immunoassay specific for isoforms containing the B chain of PDGF and a sandwich enzyme-linked immunosorbent assay specific for A-chain-containing isoforms, neither AA, nor AB, nor BB isoforms of this growth factor could be detected in medium conditioned by these cells. The absence of alterations in PDGF expression in rat mesothelioma, in contrast to the data for the human disease, suggests that the production of this growth factor by transformed mesothelial cells may be species specific.

Received 9/16/91. Accepted 11/ 1/91.

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