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Published on: April 29, 2014
Overexpression of the met/HGF receptor in renal cell carcinomas
P G Natali1, M Prat, M R Nicotra
1Regina Elena Cancer Research Institute, Rome, Italy.
Abstract:
The c-met oncogene encodes the receptor for hepatocyte growth factor/scatter factor (HGF/SF), a multifunctional cytokine able to mediate morphogenesis as well as mitogenesis, motogenesis and invasiveness of epithelial cells. HGF/SF has been implicated in branching tubulogenesis of the developing kidney and in regeneration after renal injury and nephrectomy. We have examined the expression of the met/HGF receptor in normal human kidney and tissues of the genito-urinary tract, and in 50 kidney neoplasms of different histotypes, using monoclonal antibodies (MAbs) against the met/HGF receptor and immunohistochemistry. In normal kidneys, weak staining restricted to the distal tubules was observed. Transitional cell carcinomas were consistently negative, whereas increased expression at various levels was found in 87% of renal cell carcinomas with different cytological features and histological patterns. Western blot analysis of samples showed that the met/HGF receptor found in the malignant cells exhibits features of the normal receptor. The met/HGF receptor is also overexpressed in a renal cell carcinoma cell line, whose motility is triggered by HGF/SF. Our data suggest that expression of the met/HGF receptor may be involved in the onset and progression of renal cell carcinomas.
Insights
The met/HGF receptor, involved in cell growth and movement, is often overexpressed in kidney cancers. This suggests its potential role in the development and progression of renal cell carcinomas.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The c-met oncogene encodes the receptor for hepatocyte growth factor/scatter factor (HGF/SF), a cytokine influencing epithelial cell morphogenesis, mitogenesis, motogenesis, and invasiveness.
- HGF/SF plays a role in kidney development and regeneration.
- Dysregulation of growth factor signaling pathways is common in cancer.
Purpose of the Study:
- To investigate the expression of the met/HGF receptor in normal human kidney and genito-urinary tract tissues.
- To analyze met/HGF receptor expression in various types of kidney neoplasms.
- To determine the potential involvement of the met/HGF receptor in renal cell carcinoma development and progression.
Main Methods:
- Immunohistochemistry using monoclonal antibodies against the met/HGF receptor.
- Analysis of 50 kidney neoplasms of different histotypes.
- Western blot analysis to characterize the receptor in malignant cells.
Main Results:
- Weak met/HGF receptor staining was observed in distal tubules of normal kidneys.
- Transitional cell carcinomas were negative for the receptor.
- Increased met/HGF receptor expression was found in 87% of renal cell carcinomas.
- The receptor in malignant cells showed characteristics of the normal receptor.
- Overexpression was confirmed in a renal cell carcinoma cell line, which exhibited HGF/SF-triggered motility.
Conclusions:
- The met/HGF receptor is frequently overexpressed in renal cell carcinomas.
- The expression patterns suggest a role for the met/HGF receptor in the onset and progression of kidney cancers.
- Targeting the met/HGF pathway could be a potential therapeutic strategy for renal cell carcinoma.
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