Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Adult stem cells are found in numerous tissues of the body and play a role in tissue development, replacement and repair. Evidence shows that breast stem cells are multipotent and can self renew, which are key characteristics of stem cells, and a single cell enriched with cell surface markers has the ability to grow a fully functional mammary gland in vivo. Many groups have extrapolated the cancer stem cell hypothesis from the haematopoietic system to solid cancers, where using in vitro culture techniques and in vivo transplant models have established evidence of cancer stem cells in colon, pancreas, prostate, brain and breast cancers. In the report we describe the evidence for breast cancer stem cells; studies consistently show that stem cell like and breast cancer initiating populations can be enriched using cell surface makers CD44+/CD24- and have upregulated genes which include Notch. Notch signalling has been highlighted as a pathway involved in the development of the breast and is frequently dysregulated in invasive breast cancer. We have investigated the role of Notch in a pre-invasive breast lesion, ductal carcinoma in situ (DCIS), and have found that aberrant activation of Notch signalling is an early event in breast cancer. High expression of Notch 1 intracellular domain (NICD) in DCIS also predicted a reduced time to recurrence 5 years after surgery. Using a non-adherent sphere culture technique we have grown DCIS mammospheres from primary DCIS tissue, where self-renewal capacity, measured by the number of mammosphere initiating cells, were increased from normal breast tissue. A gamma-secretase inhibitor, DAPT, which inhibits all four Notch receptors and a Notch 4 neutralising antibody were shown to reduce DCIS mammosphere formation, indicating that Notch signalling and other stem cell self-renewal pathways may represent novel therapeutic targets to prevent recurrence of pre-invasive and invasive breast cancer.

Original publication

DOI

10.1007/s12015-007-0023-5

Type

Journal article

Journal

Stem cell reviews

Publication Date

06/2007

Volume

3

Pages

169 - 175

Addresses

Breast Biology Group, Division of Cancer Studies, Faculty of Medicine and Human Sciences, University of Manchester, Paterson Institute for Cancer Research, Wilmslow Road, Manchester, M20 4BX, UK.

Keywords

Mammary Glands, Human, Mammary Glands, Animal, Spheroids, Cellular, Multipotent Stem Cells, Animals, Humans, Carcinoma, Intraductal, Noninfiltrating, Breast Neoplasms, Mammary Neoplasms, Experimental, Neoplasm Recurrence, Local, Dipeptides, Antigens, CD44, Tumor Markers, Biological, Enzyme Inhibitors, Neoplasm Transplantation, Gene Expression Regulation, Neoplastic, Up-Regulation, Female, Receptor, Notch1, Antigens, CD24, Amyloid Precursor Protein Secretases, Neoplastic Stem Cells