Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biochemistry

Supervisor

Dr. Eva Turley

Abstract

Keratinocyte carcinomas (KCs) are the most common cancers globally. Ultraviolet light is the key risk factor for these cancers but sunscreen has proven ineffective in their prevention, indicating a need for new prophylactic agents. Chronic elevation of high molecular weight (HMW) tissue hyaluronan (HA) in skin is linked to tumor resistance in the naked mole rat. To directly assess the role of this polysaccharide in resistance to keratinocyte tumors, a HMW HA phosphatidylethanolamine (HA-PE) formulation that penetrates skin and accumulates as coats around keratinocytes was prepared. The tumor resistance properties of the HA-PE formulation were tested in a mouse model of UVB-induced KC (Hr-/- Ptch+/-). HA-PE significantly reduced the number of visible lesions per mouse compared to the control groups. None of these lesions were neoplastic; in contrast, approximately 20% (7/34) of lesions were neoplastic in control groups. These results show that HA-PE protects against UVB-induced keratinocyte transformation, suggesting that HA-PE may be an effective preventative therapy for KC.

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