Seven mesothelioma cell lines, established from patients with pleural mesothelioma, exhibited substantial heterogeneity regarding in vitro morphology and growth characteristics. Media conditioned by these cell lines and by MeT5A normal mesothelial cells were examined for (i) colony formation on human bone-marrow cells, (ii) hematopoietic growth-factor content and (iii) mitogenic activity on mesothelioma cells. Colony-stimulating activity was produced only by the ZL34 cell line. Analysis of conditioned media by ELISA revealed that all mesothelioma cell lines constitutively produced IL-6, while the MeT5A normal mesothelial cells did not; in addition, GM-CSF and G-CSF were detected in the supernatant of the ZL34 cell line. Using a 3H-thymidine incorporation assay, we showed that all mesothelioma cell lines produced mitogenic activity in the culture supernatant, in contrast to the MeT5A normal mesothelial cells. The mitogenic effect of the hematopoietic growth factors detected in mesothelioma culture supernatants was tested on mesothelioma cells and on MeT5A normal mesothelial cells: IL-6, GM-CSF and G-CSF did not stimulate any DNA synthesis. Our results suggest that these hematopoietic growth factors do not act as autocrine growth factors. A common feature of this panel of mesothelioma cell lines is the production of IL-6; although the biological significance of the aberrant production of cytokines by mesotheliomas remains unclear, IL-6 might be involved in paraneoplastic syndromes such as thrombocytosis.
The pleural human mesothelioma cell line ZL5 established in our laboratory exhibits an unusual phenotype with adherent and floating cells. ZL5 cells grow in a chemically defined medium (ACL3*) and can be maintained over 3 weeks in protein-free basal medium alone (RPMI). Basal medium conditioned by ZL5 cells possesses a mitogenic activity with an autocrine effect, as measured by cell counting and by a 3H-thymidine incorporation assay. Moreover, the conditioned medium affects the DNA synthesis of a variety of other lung-derived cells. The active principle of medium conditioned by ZL5 cells is not identical to the defined growth-factors EGF, PDGF, and TGF-beta, known to stimulate the growth of normal human mesothelial cells: treatment with these factors does not mimic the effect of conditioned medium on ZL5 cells. Our observations suggest that the mesothelioma cell line ZL5 produces an unknown autocrine mitogen.
High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful research tool for the analytical separation of cellular proteins. The qualitative and quantitative pattern of polypeptides synthesized by a cell represents its phenotype and thus defines characteristics such as the morphology and the biological behavior of the cell. By analyzing and comparing the protein patterns of different cells it is possible to recognize the cell type and also to identify the most typical features of these cells. In applied pathology it is often difficult to identify the tissue of origin and the stage or grade of a neoplasia by cellular morphology analyzed by classical or immunostaining procedures. The protein pattern itself is the most characteristic feature of a cell and should therefore contribute to the identification of the cell type. For this reason we separated protein fractions originating from different lung tumor cell lines using 2-D PAGE and we compared the resulting patterns on a multivariate statistical level using correspondence analysis (CA) and ascendant hierarchical clustering (AHC). The results indicate that (i) protein patterns are highly typical for cells and that (ii) the comparison of the protein patterns of a set of interesting cell types allows the identification of potentially new marker proteins. 2-D PAGE is thus a unique and powerful tool for molecular cytology or histopathology, unveiling the protein expression level of tissues or cells.
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