Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Cheryle Séguin

Abstract

The tumor microenvironment is complex and often includes matricellular proteins and regions of hypoxia, which can promote stem and progenitor properties that regulate cancer cell biology. We hypothesized that hypoxia and CCN2 would promote notochord progenitor-like characteristics in human chordoma (U-CH1) cells, and assessed cell phenotype using Real-time qPCR and in vitro functional assays. We found the expression of CCN family members CCN1, CCN2, CCN3 and CCN5 in U-CH1 cells. We demonstrate that hypoxia and CCN2 promoted progenitor-like characteristics specific to the notochordal tissue of origin. Specifically, hypoxia had the greatest ability to promote progenitor characteristics (increase in notochord markers T, CD24, FOXA1, ACAN and CA12, sphere formation, cell growth and fewer vacuolated cells) and the effects of CCN2 were more pronounced under normoxia than hypoxia. This study highlights the importance of the tumor microenvironment and how these components can be used to regulate human chordoma behaviour.


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