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Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
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Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells
Devon A Lawson1, Nirav R Bhakta2, Kai Kessenbrock1,3
1Department of Anatomy, University of California, San Francisco, California 94143, USA.
Nature
|September 30, 2015
Summary
Early stage metastatic cells in breast cancer exhibit stem-like properties, initiating tumors and differentiating into advanced disease. This discovery supports a hierarchical model of metastasis, crucial for developing new cancer therapies.
Area of Science:
- Oncology
- Cancer Biology
- Stem Cell Research
Background:
- Metastasis is responsible for over 90% of cancer mortality.
- Understanding metastasis initiation is key to new therapeutic strategies.
- The identity of metastasis-initiating cells in human breast cancer is unknown.
Purpose of the Study:
- To identify and characterize metastasis-initiating cells in human breast cancer.
- To elucidate the hierarchical organization of metastatic tumors.
- To explore therapeutic targets for preventing metastatic progression.
Main Methods:
- Single-cell gene expression analysis.
- Development of a fluorescence-activated cell sorting (FACS)-based assay.
- Patient-derived xenograft models of human breast cancer.
Main Results:
- Early-stage metastatic cells display a stem-like gene signature, distinct from primary tumor cells.
- Metastatic cells from low-burden tissues show increased stem cell, EMT, pro-survival, and dormancy genes.
- Stem-like cells possess tumor-initiating capacity and differentiate into luminal-like cancer cells.
- Progression to high metastatic burden correlates with proliferation and MYC expression.
Conclusions:
- Metastases are initiated by stem-like cells in a hierarchical model.
- These stem-like cells proliferate and differentiate to drive advanced metastatic disease.
- Targeting proliferation and MYC may inhibit metastatic progression.
