title: Co-ordination of cell cycle, migration and stem cell-like activity in breast cancer.
abstract: Migration, proliferation and stem cell-like activity are all key cellular characteristics which aid the formation and progression of breast cancer, in addition to involvement in treatment resistance. Many current therapies aim to target tumour proliferation, and although successful, mortality rates in breast cancer remain significant. Our main objectives were to investigate the relationship between proliferation, migration and stem cell-like activity in breast cancer. We used a panel of cell lines and primary human breast cancer samples to assess the relationship between migration, proliferation and stem cells. We performed live cell sorting according to cell cycle (Hoechst-33324) and in combination with stem-cell markers (CD44/CD24/ESA) followed by assessment of migration and stem cell activity (mammosphere formation). We identified an inverse relationship between proliferation and migration/stem cell-like activity. G0/1 cells showed increased migration and mammosphere formation. Furthermore we identified a subpopulation of low proliferative stem-like cells (CD44+/24lo/ESA+) with increased migration and mammosphere formation that are specifically inhibited by Dickkopf 1 (DKK1) and Dibenzazepine (DBZ) known stem-cell inhibitors. These data show the co-ordination of migration, proliferation and stem cell activity in breast cancer, and has identified a sub-population of stem-like cells, greatly adding to our understanding of the complex nature of stem cell biology.
authors.affiliation: Breakthrough Breast Cancer Unit , Institute of Cancer Sciences, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lamb
authors.affiliation: Breakthrough Breast Cancer Unit , Institute of Cancer Sciences, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.affiliation: Breakthrough Breast Cancer Unit , Institute of Cancer Sciences, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, UK.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Clarke
authors.affiliation: Breakthrough Breast Cancer Unit , Institute of Cancer Sciences, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, UK. Center for Molecular Pathology, Department of Laboratory Medicine, Lund university, Skåne University Hospital, Malmö, Sweden. Sahlgrenska Cancer Center, University of Gothenburg, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Landberg
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology*