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Organic anion transporter 1B3 as a therapeutic target of recessive dystrophic epidermolysis bullosa associated squamous cell carcinoma (South 1)

Completed
Project lead Dr Andrew South
Organisation University of Dundee School of Medicine, Ninewells Hospital and Medical School
Project budget EUR 58,996.00
Start date / Duration 01. Jan 2011 / 12 months
Funder(s) / Co-Funder(s) DEBRA Austria, MSAP/EBEP Recommended
Research area Skin cancer & fibrosis

Project details

Short lay summary

The advances in EB care have led to improved quality of life for many patients. Unfortunately sufferers of dystrophic EB develop skin cancer that is life threatening, the reasons for which remain unclear. Efficient ways to treat this complication of the disease are needed. Through DebRA funded research our lab have identified a protein expressed in EB cancers. The protein is called OATP1B3 and functions to transport organic solutes and many drugs from the blood stream into the liver and is normally exclusively expressed in the liver. However, it has become clear from recent literature that OATP1B3 is also found in colon, lung and breast cancers. As a protein capable of introducing drugs and compounds into cells, OATP1B3 has been targeted as a potential route for cancer therapy. Our own research shows that normal copies of the gene damaged in dystrophic EB, COL7A1, reduces the expression of OATP1B3 in EB skin cancer cells. Our hypothesis is that OATP1B3 expression contributes to the aggressive nature of EB skin cancer and that we can use this expression to target these cancers. We plan to establish the extent of OATP1B3 expression in EB skin cancers; validate OATP1B3 as an active transporter with the ability to selectively kill EB skin cancer cells; determine the nature of COL7A1 regulation of OATP1B3; and investigate the mechanism of cancer cell survival resulting from OATP1B3 expression.

What did this project achieve?

We have been able to establish that OATP1B3 is highly expressed in both dystrophic EB and UV induced skin cancers. We show that the expression of OATP1B3 is modulated by COL7A1 (the gene mutated in dystrophic EB) in skin cancers from dystrophic EB and non-EB individuals. We have also established that OATP1B3 can effectively mediate the transport of drugs and toxins into EB cancer cells. Our findings will require further validation to achieve clinical utility but, based on the outcome of this project, we are hopeful that OATP1B3 may be a therapeutic target in EB skin cancer.


Keywords

dystrophic EB
RDEB
SCC
South 1
South
Dundee
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