Pathological and immunological analysis of RDEB-SCC for the development of novel biomarkers (Marshall 4)Completed
|Project lead||Dr John Marshall|
|Organisation||Queen Mary University of London, Centre for Cell Biology and Cutaneous Research, London, UK|
|Project budget||EUR 119,228.00|
|Start date / Duration||01. Apr 2010 / 24 months|
|Funder(s) / Co-Funder(s)||DEBRA Austria, MSAP/EBEP Recommended|
|Research area||Skin cancer & fibrosis|
Short lay summary
For many years the EB research community has been unable to determine why squamous cell carcinoma in RDEB patients have a metastatic propensity (and kill patients) compared with non-EB SCC which is rarely metastatic. Since development of SCC in RDEB is usually associated with chronic wound healing this suggests that this host response provides a permissive environment for cancer to develop and spread. Whereas others have concentrated on the transformed keratinocytes in SCC we shall use a non-candidate approach to examine the stroma of RDEB SCC. Thus to identify biomarkers associated with the EB-SCC we will 1) use expression proteomic analysis of stromal isolated using PALM laser dissection 2) incubate EB-SCC tissues with scFv antibody phage libraries and identify those stromal proteins differentially expressed in the EB-SCC tumour stroma versus normal skin or non-EB SCC 3) for the first time we shall undertake a systematic histopathological analysis of EB-SCC versus non-EB SCC archival tissues that will direct immunopathology analysis of the tumour-associated environment (stromal fibroblasts, EMT, angiogenesis, protease activity as inflammatory infiltrate). These data, which will be collated as a database for the EB community, should identify factors associated specifically with EB-SCC.
All cancers develop by talking to the normal cells that surround them. In some instances, they send signals to this ‘microenvironment’ which can result in some of these completely normal cells changing their behaviour in such a way that it actually helps the cancers to grow faster and spread more easily. So modern cancer therapy must consider stopping both the cancer cells AND those normal cells that produce factors that help the cancer cells. The skin cancers that develop in EB patients, especially those with RDEB, tend to develop more frequently and then spread more easily than similar types of skin cancer that develop in people without EB. Colleagues have found however that the actual skin cancer cells themselves in people with EB and without EB are extremely similar. Thus we considered that the reason the cancers in EB patients do worse is that the response of their microenvironment is different. We believe that the proteins produced in the microenvironment are different in skin cancers from EB patients compared with non-EB patients and that one or more of these proteins may help the EB cancers to spread more easily. Therefore we have use 2 techniques to study this possibility.