EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR (PDGF) AND PDGF RECEPTORS IN HUMAN-MALIGNANT MESOTHELIOMA IN-VITRO AND IN-VIVO

The expression of platelet-derived growth factor (PDGF) and PDGF recep tors was studied in human normal and malignant mesothelial cells in vi tro and in vivo. Staining with anti-cytokeratin and ME1 antibodies and ultrastructural analysis confirmed the mesothelial nature of the cell lines used to study PDGF and PDGF receptor expression in vitro. Using antibodies, mesothelioma cell lines were found to express PDGF and bo th the PDGF alpha- and the PDGF beta-receptor, whereas cultured normal mesothelial cells expressed PDGF and PDGP alpha-receptor. This PDGF a nd PDGF receptor staining pattern largely reflects the earlier describ ed mRNA expression in these cell lines. The only exception was the imm unocytochemical detection of PDGF alpha-receptors in the mesothelioma cell lines, which is different from the inability to detect alpha-rece ptor transcripts on Northern blots. Expression was also investigated i n mesothelial cells in vivo. Expression of PDGF was observed in malign ant mesothelioma cells on frozen tissue sections. In pleural effusions , a double immunofluorescence staining procedure for PDGF and epitheia l membrane antigen (EMA) revealed PDGF expression by EMA-positive mali gnant mesothelioma cells. PDGF beta-receptors and occasionally PDGF al pha-receptors mere detected in frozen tissue sections of malignant mes otheliomas, whereas mesothelioma cells in effusions showed faint expre ssion of only the PDGF beta-receptor. In contrast, in effusions contai ning non-malignant mesothelial cells, only a very low level of PDGF al pha-receptor could be detected. Taken together, these results indicate that the pattern of PDGF and PDGF receptor expression in mesothelial cells in vivo largely corresponds to expression of PDGF and its recept ors in vitro. Malignant mesothelioma cell lines thus constitute a good model system for studies on the role of PDGP in this malignancy. Furt hermore, the data reported hi this paper are consistent with the idea that an autocrine growth stimulatory effect of PDGF via PDGF receptors may play a role in the pathogenesis of malignant mesothelioma.