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Expression of the transmembrane protein tyrosine phosphatase RPTPalpha in human oral squamous cell carcinoma
1Institute of Pathology, Friedrich Schiller University, Jena, Germany. berndt@bach.med.uni-jena.de
Abstract:
Little is known about the role of protein-tyrosine phosphatases (PTPs), the cellular counterparts of protein-tyrosine kinases, both for normal growth regulation and for its dysregulation in cancer. The receptor-like PTPalpha (RPTPalpha) may play a positive role in growth regulation and has been shown to be overexpressed in colon carcinoma. An RNA/RNA in situ hybridisation protocol for RPTPalpha as well as RPTPalpha immunohistochemistry was developed to evaluate RPTPalpha expression in oral squamous cell carcinomas (OSCCs) of different histological grade and to reveal the synthetically active cells and their tissue distribution. In well-differentiated OSCC (G1), RPTPalpha mRNA could be detected by in situ hybridisation exclusively in stroma cells (fibro/myofibroblasts and inflammatory cells). A higher histological grade (G2/G3) was associated with an increased number of RPTPalpha-synthesising carcinoma cells haphazardly distributed within invading tumour areas. Consistent results were obtained by immunocytochemistry. Thus, both carcinoma dedifferentiation and stroma recruitment and activation seem to be associated with an upregulation of RPTPalpha expression in OSCC. The results speak in favour of the important role of activation of stroma fibro/myofibroblasts influencing the biological behaviour of epithelial tumours and also suggest that elevated RPTPalpha expression may be a more general marker for proliferating or dedifferentiated cells.
Insights
Protein-tyrosine phosphatases (PTPs) like RPTPalpha are crucial in cancer. This study found RPTPalpha expression increases with oral squamous cell carcinoma (OSCC) dedifferentiation and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Protein-tyrosine phosphatases (PTPs) are key regulators of cell signaling, analogous to protein-tyrosine kinases.
- The receptor-like PTPalpha (RPTPalpha) is implicated in growth regulation and has been observed to be overexpressed in colon carcinoma.
- Understanding RPTPalpha's role in oral squamous cell carcinomas (OSCCs) is limited.
Purpose of the Study:
- To investigate the expression patterns and cellular distribution of RPTPalpha in OSCCs of varying histological grades.
- To determine the association between RPTPalpha expression, tumor dedifferentiation, and stromal cell activity in OSCC.
- To assess RPTPalpha as a potential marker for proliferating or dedifferentiated cells in epithelial tumors.
Main Methods:
- Development of RNA/RNA in situ hybridization and immunohistochemistry protocols for RPTPalpha.
- Evaluation of RPTPalpha mRNA and protein expression in different histological grades of OSCC.
- Correlation of RPTPalpha expression with histological grade, cellular differentiation, and stromal cell populations.
Main Results:
- In well-differentiated OSCC (G1), RPTPalpha mRNA was localized to stromal cells (fibro/myofibroblasts and inflammatory cells).
- Higher histological grades (G2/G3) showed increased RPTPalpha synthesis in dedifferentiated carcinoma cells within invasive tumor areas.
- Immunohistochemistry confirmed these findings, indicating consistent RPTPalpha upregulation in more aggressive OSCC.
Conclusions:
- Carcinoma dedifferentiation and stromal cell activation are associated with increased RPTPalpha expression in OSCC.
- Activated stromal fibro/myofibroblasts play a significant role in the biological behavior of epithelial tumors.
- Elevated RPTPalpha expression may serve as a general biomarker for proliferating or dedifferentiated cells in various cancers.