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An autocrine mitogenic activity produced by a pleural human mesothelioma cell line
B Lauber1, M Leuthold, D Schmitter
1Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland.
Abstract:
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.
Insights
The ZL5 mesothelioma cell line produces an unknown growth factor that stimulates its own proliferation. This autocrine mitogen also impacts other lung cells, suggesting a novel mechanism in mesothelioma.
Area of Science:
- Oncology
- Cell Biology
Background:
- The ZL5 human pleural mesothelioma cell line displays a unique dual phenotype (adherent and floating cells).
- ZL5 cells can be cultured in a chemically defined medium (ACL3*) or protein-free basal medium (RPMI).
Purpose of the Study:
- To investigate the mitogenic activity present in the conditioned medium of the ZL5 mesothelioma cell line.
- To identify the nature of the growth-promoting factor produced by ZL5 cells.
Main Methods:
- Cell counting assays to measure proliferation.
- 3H-thymidine incorporation assays to assess DNA synthesis.
- Testing the effects of known growth factors (EGF, PDGF, TGF-beta) on ZL5 cells.
Main Results:
- ZL5 cell-conditioned medium exhibits significant mitogenic activity on ZL5 cells, indicating an autocrine effect.
- The conditioned medium also influences DNA synthesis in other lung-derived cells.
- Established growth factors (EGF, PDGF, TGF-beta) do not replicate the mitogenic effect of the ZL5 conditioned medium.
Conclusions:
- The ZL5 mesothelioma cell line produces an unidentified autocrine mitogen.
- This novel mitogen may play a role in mesothelioma progression and affects other lung cells.