Al-Hajj 2003: prospective identification of tumorigenic breast cancer cells
The first demonstration in a solid tumour that only a small, marker-defined fraction of breast cancer cells can regrow the cancer: a few hundred cells with one surface profile formed tumours in mice while tens of thousands of the other cells did not.
Overview
Al-Hajj, Wicha, Clarke and colleagues separated cells from human breast cancers, mostly metastatic fluid collections and one primary tumour, by surface markers and injected them into immunodeficient mice. Cells that were CD44-positive and CD24-negative or low, and lacked lineage markers, formed tumours from as few as 100 cells in eight of nine patients' samples, whereas tens of thousands of cells with other profiles did not. The resulting tumours reproduced the mixture of cell types of the original cancer and could be passaged serially, the defining behaviour of a cancer stem cell.
- Tumorigenic cells from human breast cancers were enriched in the CD44-positive, CD24-negative or low, lineage-negative fraction.
- As few as 100 such cells formed tumours in NOD/SCID mice; tens of thousands of cells with other marker profiles did not.
- Tumours from the sorted cells reproduced the original tumour's heterogeneity and could be passaged repeatedly.
This paper extended the cancer stem cell concept from leukaemia to a common solid tumour and started the search for tumour-initiating cells across cancers. It underpins research on why cancers relapse after treatments that shrink them and on therapies aimed at the cells that regrow disease.
- Samples were mostly metastatic effusions rather than primary tumours.
- Transplantation into mice measures what survives the assay and may not reflect behaviour in patients.
- The markers are not universal across breast cancer subtypes.
Similar pages
not linked directly; found by shared links- Key paperBao 2006: glioma stem cells resist radiotherapy by activating the DNA damage response
Shares Reya 2001: stem cells, cancer and cancer stem cells, Recurrence and relapse, Stem cell.
- PersonLori J. Pierce
Shares University of Michigan Rogel Cancer Center, Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer.
- PathwayTumour dormancy
Shares Recurrence and relapse, Stem cell, HR-positive / HER2-negative breast cancer.
- PathwayEpithelial-mesenchymal transition & drug efflux
Shares Max S. Wicha, Mani 2008: the epithelial-mesenchymal transition generates cells with properties of stem cells, Triple-negative breast cancer (TNBC).