Role of High Molecular Weight Hyaluronan in Ultraviolet B Light-Induced Transformation

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.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Biochemistry

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2017

Author dc:creator

• Cousteils, Katelyn

Advisor dc:contributor.advisor

• Eva Turley

• cancer
• hyaluronan
• inflammation
• keratinocyte
• naked mole rat
• phosphatidylethanolamine
• skin
• ultraviolet

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/27830

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/27830