Characterization of cancer stem cell sub-populations in melanoma
Stephanie Lunt will be working at Queen Mary University of London using patient cancer samples to identify biomarkers in skin cancer (melanoma) to help replace the use of mice.
SUPERVISOR: Dr Adrian Biddle – at the Animal Replacement Centre, Queen Mary University of London
STUDENT: Miss Stephanie Lunt
Melanoma is among the most aggressive cancers, with poor survival and limited treatment options. Cancer stem cells, the sub-population of cancer cells that drive long-term tumour growth, provoke intense interest due to their heightened resistance to therapy and ability to seed the metastatic growths that cause 90% of all cancer deaths.
Identification and characterization of these cells, so that therapies can be developed to target them, is a priority in cancer research. The majority of studies use mouse transplantation of human cancer cells for these investigations, and we are developing methods for the replacement of mice in these studies. In cell culture of human melanoma cell lines, we have identified an aggressive cancer stem cell sub-population with behaviours suggesting it may be responsible for tumour metastasis and therapeutic resistance.
This Summer project will initiate the next important step of this study – to validate our cell culture findings using preserved human melanoma specimens in order to test whether the findings of our cell culture model can be directly translated to human cancer. This important validation step is needed to demonstrate the relevance of our cell culture model to human cancer and thereby encourage expanded use by the scientific community of our cell culture model in preference to mouse models.
In the UK, animal studies involve the transplantation of human cancer cells into mice followed by observation of primary and metastatic tumour growth, typically with the use of 25-50 mice per study. The severity level is classed as moderate and, globally, around 150 academic studies of this type are published each year for melanoma. Mouse models are slow, expensive, and provide a paucity of useful data. The over-dependence on mouse models has slowed progress in cancer research, and has often provided misleading data that does not hold for human cancer (Voskoglou-Nomikos et al., 2003). There is therefore a pressing need for cell culture models that have demonstrable relevance to human cancer.
Reference: Voskoglou-Nomikos, T., et al., Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res 2003; 9(11): 4227-4239.