Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Silvia Penuela

Abstract

Pannexin 1 (PANX1) is a channel-forming glycoprotein that allows the passage of important signaling molecules, including ATP. We examined PANX1 levels in a panel of human melanomas and evaluated its potential as an effective target for melanoma therapy. We are the first to report endogenous PANX1 levels in multiple human melanoma cell lines, patient-derived melanoma biopsies, and primary melanoma cells. Treatment with two PANX1 channel blockers, Carbenoxolone (CBX) and Probenecid (PBN), on A375 and A375-MA2 melanoma cells significantly reduced cell growth and migration, and increased the production of melanin, a marker for a melanocytic-like phenotype. Daily treatment with CBX or PBN onto A375-MA2 cells grown on the chorioallantoic membrane of a chicken embryo model significantly reduced primary melanoma tumour growth. Our findings suggest a possible dysregulation of PANX1 in human melanomas that may contribute to malignant behaviour and provides support for PANX1 channel blockers as a potential treatment for melanoma.

Available for download on Saturday, July 20, 2019


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