Genito-urinary cancer: stem cell research
There has been considerable interest in haematopoietic stem cells for over 40 years since Till and McCulloch (1961) demonstrated clonogenic bone marrow precursors could generate multilineage haematopoietic colonies in the spleen. Recently it has been shown that normal haematopoietic stem cells are the targets for leukaemic transformation in human acute myeloid leukaemia (AML). In common with many other tissues it is believed that organs of the genito urinary tract harbour stem cells. Observations, similar to those in haematopoietic systems, have shown that between 1 in 1000 to 1in 5000 lung cancer, ovarian cancer or neuroblastoma cells form clonies in a soft agar assay, which has led to the hypothesis that only a minority of cancer cells are tumourigenic and are cancer stem cells. We are interested in epithelial tumours of the genito urinary tract, prostate, renal and bladder tumours, and the potential role of specific organ stem cells in malignancy.
Prostate
In the prostate stem cell have been implicated in the development of prostate cancer. However the isolation of prostate epithelial stem cells has been hampered by the lack of specific markers able to isolate the stem cell population. We have recently published that the Hoechst 33342 dye efflux assay can be adapted for the isolation of a side population (SP) from both non-malignant and malignant primary prostate tissue (ref 2). This SP population accounts for 1.38% ± 0.07% of the prostate epithelial cell population and consists of cells in either G0 or G1. The nature of these SP cells are currently being defined.
See: Figure 1
Kidney
Incidence of renal cancer in the UK is approximately 6000 cases per annum with a resulting mortality rate of 3200 cases per year (Cancer Research UK). It has been shown that a single metanephric mesenchymal cell from a developing kidney can generate all the epithelial cell types of the nephron, bar the collecting duct. It is unknown whether these stem cells are retained in the mature kidney. We aim to adapt prostate derived SP protocols to isolate stem cells from normal and malignant renal tissue and define their role in malignant disease.
Bladder
Incidence of bladder cancer in the UK is approximately 12000 cases per annum with a resulting mortality rate of 5000 cases per year (Cancer Research UK). Over 90% of bladder cancers are transitional cell carcinomas, which are an epithelial tumour. We aim to adapt prostate derived SP protocols to isolate stem cells from normal and malignant bladder tissue and define their role in malignant disease.