chondroitin-sulfates and Mesothelioma

Two human malignant mesothelioma cell sublines, one with a fibroblast-like and the other with an epithelial differentiation, were examined for their capacity to synthesize glycosaminoglycans in the presence of IGF-I, EGF, and their combination. This synthesis depends on the morphology of the mesothelioma cells, with many-fold higher amounts of both hyaluronan and proteoglycans being produced by the cells with epithelial morphology than by those of the fibroblast phenotype. In both cell lines this synthesis was affected in a dose-dependent fashion by the exogenously added growth factors and exposure to IGF-I and EGF in combination showed a synergistic effect. This effect of those factors seems to be mediated via protein tyrosin kinase-dependent receptors and was different in the fibroblast-like and epithelial cells. The synthetic rates of the various glycosaminoglycans formed (hyaluronan, galactosaminoglycans and heparan sulfate) were also variously affected by these factors, indicating differences in how the synthesis of the various glycosaminoglycans is regulated. The results obtained suggest a close correlation between the presence of the appropriate growth factor(s), the process of cell differentiation and the synthesis of glycosaminoglycans in these cells.

Topics: Chondroitin Sulfates; Drug Interactions; Enzyme Inhibitors; Epidermal Growth Factor; Epithelial Cells; Epithelium; Fibroblasts; Genistein; Glycosaminoglycans; Humans; Hyaluronic Acid; Insulin; Insulin-Like Growth Factor I; Isoflavones; Mesothelioma; Proteoglycans; Receptor Protein-Tyrosine Kinases; Signal Transduction; Tumor Cells, Cultured

Using a modified papain digestion cetylpyridinium salt precipitation method, glycosaminoglycans were isolated from 21 mesotheliomas, 34 primary lung carcinomas, 12 carcinomas of other sites, and 7 soft tissue sarcomas. Qualitatively, hyaluronic acid (HA) was present in 20 of 21 mesotheliomas, about half of the primary lung adenocarcinomas, and all of the soft tissue sarcomas. On the average, HA constituted 45% of the total glycosaminoglycans in the mesotheliomas and 28% of the total in the lung cancers. Quantitatively, mesotheliomas contained statistically greater amounts (mean value, 0.74 mg/g) of HA than primary lung adenocarcinomas (mean value, 0.08 mg/g), but were not statistically different from soft tissue sarcomas (mean value, 2.01 mg/g) or primary ovarian serous neoplasms (mean value, 0.92 mg/g). The study concludes that, contrary to previous reports, HA is neither the sole nor the predominant glycosaminoglycan in most mesotheliomas, but, given the proper clinical and histologic setting, the finding of sufficiently high levels (greater than 0.4 mg/g dry tissue extract) supports the diagnosis of mesothelioma when the alternative diagnosis is primary adenocarcinoma of lung.

Topics: Adenocarcinoma; Carcinoma; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Electrophoresis, Cellulose Acetate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Lung Neoplasms; Mesothelioma; Ovarian Neoplasms; Sarcoma

Glycosaminoglycans of a malignant pleural mesothelioma have been characterized histochemically and biochemically and compared with those of normal lung, pleural plaque, lung carcinoma, and other connective tissue neoplasms. Chondroitin sulfate constituted the major glycosaminoglycan (approximately 80% of total) present in the pleural mesothelioma while hyaluronic acid was present in only trace amounts (approximately 3% of total). In particular chondroitin 6-sulfate was the predominant isomer, constituting 80% of the total chondroitin sulfate. Control tissue exhibited different proportions of glycosaminoglycans and none of them contained as high an absolute concentration of chondroitin sulfate as the mesothelioma. These findings differ from previous reports demonstrating increased concentration of hyaluronic acid in mesothelioma and suggest the possible existence of a biochemically different form of this neoplasm.

Topics: Aged; Asbestos; Chondroitin Sulfates; Glycosaminoglycans; Humans; Hyaluronic Acid; Lung; Lung Neoplasms; Male; Mesothelioma; Pleural Neoplasms