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Tumorigenic conversion of human mesothelial cells as a consequence of platelet-derived growth factor-A chain
A Van der Meeren1, M B Seddon, C A Betsholtz
1Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Abstract:
Overexpression of platelet-derived growth factor (PDGF)-A as well as PDGF-B chain mRNA has previously been reported in human mesothelioma cell lines. In this report, it has been established that the A but not the B chain protein is expressed at detectable levels in cell lysates and conditioned medium from these cell lines. In order to investigate the effect of overexpression of PDGF-A chain in a human mesothelial cell model system, a retroviral vector containing a human PDGF-A chain cDNA insert under the control of the Moloney murine leukemia virus (MoMLV) promoter was inserted into the SV-40 T-antigen immortalized human mesothelial cell line MeT-5A. Selected cells showed overexpression of PDGF-A chain relative to MeT-5A and induced tumors in athymic nude mice. PDGF-A chain overexpression was also found in the tumor specimens excised from the mice. PDGF-A mRNA and protein were expressed at a higher level in the tumor explant cell lines, suggesting a correlation of tumorigenicity with A chain production.
Insights
Overexpression of platelet-derived growth factor (PDGF)-A protein in human mesothelial cells promotes tumor growth. This study demonstrates a link between PDGF-A chain production and increased tumorigenicity in a mesothelial cell model.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Platelet-derived growth factor (PDGF)-A and -B mRNA are overexpressed in human mesothelioma cell lines.
- PDGF-A protein, but not PDGF-B, is detected in mesothelioma cell lysates and conditioned medium.
Purpose of the Study:
- To investigate the effect of PDGF-A chain overexpression in a human mesothelial cell model.
- To establish a correlation between PDGF-A chain production and tumorigenicity.
Main Methods:
- A retroviral vector with human PDGF-A chain cDNA was used to overexpress PDGF-A in the MeT-5A human mesothelial cell line.
- Cells were selected for PDGF-A overexpression and xenografted into athymic nude mice.
- Tumor specimens and explant cell lines were analyzed for PDGF-A expression.
Main Results:
- Overexpression of PDGF-A chain was successfully achieved in MeT-5A cells.
- PDGF-A overexpression led to tumor formation in athymic nude mice.
- Elevated PDGF-A mRNA and protein levels were observed in tumors and tumor explant cell lines, correlating with tumorigenicity.
Conclusions:
- PDGF-A chain overexpression in human mesothelial cells contributes to tumorigenicity.
- The study suggests a direct correlation between PDGF-A production and the development of mesothelioma tumors.