Investigating the role of hydrogen sulfide in the survival, growth and angiogenic potential of clear cell renal cell carcinoma cell lines and xenografts

Author

Eric Sonke, The University of Western OntarioFollow

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Alp Sener

Abstract

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H₂S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H₂S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism, and angiogenesis. Using H₂S-specific probes, it was found that H₂S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H₂S-producing enzymes could reduce the proliferation, metabolism and survival of ccRCC cell lines, as determined by live-cell imaging, XTT/ATP assay, and flow cytometry, respectively. Using the chorioallantoic membrane angiogenesis model, it was found that systemic inhibition of endogenous H₂S production was able to decrease vascularization of VHL-deficient ccRCC xenografts. Endogenous H₂S production is an attractive new target in ccRCC due to its involvement in multiple aspects of disease.

Recommended Citation

Sonke, Eric, "Investigating the role of hydrogen sulfide in the survival, growth and angiogenic potential of clear cell renal cell carcinoma cell lines and xenografts" (2015). Electronic Thesis and Dissertation Repository. 2879.
https://ir.lib.uwo.ca/etd/2879