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c-Met ectodomain shedding rate correlates with malignant potential.
Gagani Athauda1, Alessio Giubellino, Jonathan A Coleman
1Urologic Oncology Branch, Laboratory of Molecular Pharmacology, and Medical Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-1107, USA.
Summary
Increased ectodomain shedding of the c-Met receptor tyrosine kinase correlates with malignant potential in cancer. Measuring soluble c-Met may serve as a biomarker for tumor progression and burden.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ectodomain shedding is a physiological process where proteins are cleaved from the cell surface.
- c-Met, the receptor tyrosine kinase for hepatocyte growth factor (HGF), plays a role in development and tissue regeneration.
- Dysregulated HGF signaling is implicated in various human cancers, often involving c-Met overexpression.
Purpose of the Study:
- To investigate the hypothesis that c-Met overexpression in cancer leads to increased ectodomain shedding.
- To explore the potential of measuring c-Met ectodomain shedding as a biomarker for tumor progression.
Main Methods:
- Development of a sensitive electrochemiluminescent immunoassay to quantify c-Met protein.
- Analysis of c-Met shedding in cell lysates, culture supernatants, and biological samples.
Main Results:
- Significant positive correlations were observed between malignant potential and the rate of c-Met ectodomain shedding in cancer cell models.
- Soluble c-Met levels in plasma and urine of mice with human tumor xenografts correlated directly with tumor volume and were detectable before tumors were palpable.
Conclusions:
- c-Met ectodomain shedding can serve as a reliable indicator of malignant potential in various human cancers.
- Measuring soluble c-Met may offer a practical approach to assess overall tumor burden.