# Al-Hajj 2003: prospective identification of tumorigenic breast cancer cells

Source: https://onco.cc/key-papers/paper-al-hajj-breast-cancer-stem-cells-pnas-2003/  
OnCo record `paper-al-hajj-breast-cancer-stem-cells-pnas-2003` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: Proceedings of the National Academy of Sciences
- Year: 2003
- DOI: 10.1073/pnas.0530291100
- Authors: Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF.
- Findings: 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.
- What it means: 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.
- Caveats: 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.

## Sources

- Full text (DOI): https://doi.org/10.1073/pnas.0530291100

## Connected records

- key papers: [Mani 2008: the epithelial-mesenchymal transition generates cells with properties of stem cells](https://onco.cc/key-papers/paper-mani-emt-stem-cell-properties-cell-2008/), [Reya 2001: stem cells, cancer and cancer stem cells](https://onco.cc/key-papers/paper-reya-cancer-stem-cells-nature-2001/)
- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- institutions: [University of Michigan Rogel Cancer Center](https://onco.cc/institutions/michigan-rogel/)
- terms: [Cancer stem cell theory and phenotypic plasticity](https://onco.cc/terms/cancer-stem-cell-theory/), [Recurrence and relapse](https://onco.cc/terms/relapse-recurrence/), [Stem cell](https://onco.cc/terms/stem-cell/)
- people: [Max S. Wicha](https://onco.cc/people/max-wicha/)

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