Breast Cancer Stem Cells Group led by Dr Robert Clarke
Our research aims to understand the hierarchical relationship between cells in breast epithelium – working out the rank and order of cells and cell processes and how they interact or communicate – in order to elucidate how cancer is initiated in breast tissue. We focus on understanding how stem cells are regulated as these cells are likely to be the first (or at least very early) players in cancer initiation. We also want to understand how steroid hormones such as oestrogen regulate this hierarchy, since both normal and tumour development is hormone dependent.
Breast tissue is made up of collecting ducts and lobules both of which develop from two distinct types of stem cells, muscle-like epithelial cells and milk-producing luminal cells, respectively. Our group have developed new methods for the isolation and characterisation of the putative breast epithelial stem cells that give rise to these two cell types. One current interest is which of the Notch, Hedgehog, Wnt, TGFbeta, EGF and other relevant signalling pathways regulate stem cell self-renewal. We are also exploiting gene analysis methods (such as gene expression arrays and functional genomics) to identify genes that are active in novel pathways of stem cell regulation.
Identification of stem cell self-renewal pathways may be important for future cancer prevention and therapy: an emerging concept is that in leukaemia as well as in neural and epithelial cancers, including breast cancer, only a minority of cells, i.e. the “cancer stem cells”, are able to initiate tumours. It is possible that dysregulation of the self-renewal process plays a role in cancer development. Thus, understanding the cancer stem cell and the molecular basis for dysregulated self-renewal is important for identification of potential therapeutic targets and the micrometastases (small numbers of cancer cells that have spread from the primary tumour site to other sites of the body and are too few to be picked up in routine screening or diagnostic tests) which can initiate tumours.
Another approach we are investigating is how to identify early changes that occur in normal and premalignant tissues and predict the emergence of a tumour. If these changes can be detected and prevented, then it may be possible to reduce the incidence of breast cancer. The results of these investigations should lead to an increased understanding of the biology of the normal human breast which, in turn, could lead to the development of new strategies or new targets for breast cancer prevention and therapy.
Find out more
The Breast Cancer Stem Cells Group is part of the Manchester Breast Centre, an amalgamation of key breast cancer research groups formed in 2005 and sited in five major centres for medical and life science research across Manchester. The Breast Cancer Stem Cells Group is based in the Faculty of Medical & Human Sciences within The University of Manchester and is part of the Paterson Institute for Cancer Research which became part of The University of Manchester in 2006. Find out more about the work of the Breast Cancer Stem Cells Group and key publications.