Stimulatory effects of pleural fluids from mesothelioma patients on CD44 expression, hyaluronan production and cell proliferation in primary cultures of normal mesothelial and transformed cells

Cell lines established from human malignant mesotheliomas, but not from normal mesothelial cells, have been shown to possess hyaluronan receptors, and to secrete factors that stimulate hyaluronan production by fibroblasts and normal mesothelial cells. In the present study we investigated the generality of this observation, namely the presence of hyaluronan receptors and factors which induce stimulation of hyaluronan synthesis in primary mesothelioma and mesothelial cell cultures. Functionally active hyaluronan- binding sites on the surface of malignant mesothelioma cells in primary cultures, established from pleural effusions of 3 different patients, were demonstrated using ³H-hyaluronan. Primary cultures of normal mesothelial cells from non-mesothelioma effusions did not exhibit any binding ability. Pleural fluids from mesothelioma patients both stimulated hyaluronan synthesis and promoted proliferation of normal mesothelial cells to a larger extent than non-mesothelioma fluids. The hyaluronan-stimulatory activity was only slightly neutralized by antibodies against PDGF-BB or TGF-β; antibodies against bFGF had no effect. Although the concentration of hyaluronan was much higher in pleural fluids from mesothelioma than from non-mesothelioma patients, its molecular weight was almost the same. The hyaluronan-binding capacity of early-passage mesothelioma cells derived from pleural effusions can be an additional marker, in combination with other diagnostic tools, to distinguish between mesothelioma and mesothelial cells.