Professor Irene Leigh, Queen Mary University of London; CRUK, London Research Institute: Lincolns Inn Fields; CRUK, London Research Institute: Clare Hall Laboratories
Non-melanoma skin cancers (NMSCs or Keratinocyte cancers-KC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), receive less awareness than their melanoma counterpart. This is because they are perceived as causing fewer deaths, as only SCCs metastasise. However, the incidence of NMSC is very high (18-20 times higher than that of melanoma) and there are 156,000 new non-melanoma skin cancer cases in the UK every year (2016-2018) – almost 430 every single day. Non-melanoma skin cancers commonly develop due to the skins exposure to the sun. Because these cancers are caused by excessive ultraviolet radiation, patients often end up having more than one skin cancer, resulting in multiple surgeries. Both types of carcinoma have an excellent prognosis, are slow-growing and rarely metastasise, however, in some cases they can develop into invasive skin cancers, with an aggressive nature.
It is critical to study NMSCs to produce diagnostic tests which identify high-risk tumours for metastasis and progression and generate treatments which limit carcinoma recurrence, as this is more challenging to treat.
One group of patients that are significantly affected by SCC and BCC are the immunosuppressed. With over 40% of SCC mortalities occurring in organ transplant receivers, this group has an important impact on immunotherapy treatment options and survivability. In working with these patients, Professor Leigh and her team have established a unique panel of patient-derived cutaneous squamous cell carcinoma cell lines. One example from this panel is the MET1 SCC cell line.
This cell line was derived from a primary lesion on the hand of an immunosuppressed patient, which ultimately recurred (MET2 cell line) and metastasised (MET4SCC line), representing crucial stages in SCC transformation. Understanding the stages a squamous cell carcinoma takes in order to become increasingly invasive helps dictate preventative and therapeutic measures for this cancer. This cell line has also been used in a variety of research; from indicating HPV isn’t essential for cancerous phenotype maintenance, to furthering our understanding of epithelial-mesenchymal transition within metastasis.
RDEB is a debilitating condition involving a deficiency in anchoring fibrils, predominantly type VII collagen – between the epidermis basement membrane and underlying connective tissue. This leads to extremely fragile skin with severe blistering, meaning most patients develop SCC before the age of 35. Irene and her team helped to uncover the genetic basis of this condition through their research.
Anti-Collagen Type VII LH7.2 is a monoclonal antibody which binds to an epitope of type VII collagen within the basement membrane of stratified squamous epithelia. This antibody helps diagnose RDEB as LH7.2 binding is absent or significantly reduced in RDEB patients. LH7.2 can also be used for differentiating invasive from non-invasive melanoma by assessing the integrity of epidermal basement membranes. This enables us to predict how aggressive SCC might be in RDEB patients.
Professor Leigh and her team also created a monoclonal antibody that could be used to diagnose SCC and BCC tumours. Keratins 5, 6 are members of the type II keratins family that are specifically expressed in the inner root sheath of hair follicles. Keratins demonstrate tissue and differentiation-specific expression profiles. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains co-expressed during differentiation of simple and stratified epithelial tissues. Keratin 18 is a member of the type I intermediate filament chain keratin 18. Keratin 18, together with its filament partner keratin 8, are perhaps the most commonly found members of the intermediate filament gene family. These cytokeratins have been reported to be expressed in tumour cells of epithelial origin and less commonly of mesothelial origin- however, non-epithelial tumours, e.g. lymphomas, do not express these cytokeratins. Anti-Katine 5/6/18 LP34 identifies tumours with an epithelial origin and is key in pathological diagnosis and understanding metastases. As this antibody binds to keratins 5, 6 and 18, it can also be used to identify uncultured keratinocyte material. Polyspecific LP34 also has an uncommonly broad pattern of reactivity, staining all human epithelial cells - both stratified and simple epithelium.
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About Professor Irene Leigh
Professor Irene Leigh is currently a professor of Cellular Molecular Medicine at Barts and the London School of Medicine and Dentistry, Queen Mary University London. Leigh established the Centre for Cutaneous Research at Barts and The London School of Medicine and Dentistry, Queen Mary University of London (BLSMD) which went on to become the leading research centre in skin biology and disease in the United Kingdom.