期刊
ONCOTARGET
卷 6, 期 12, 页码 10366-10373出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3590
关键词
breast cancer; tumour cell heterogeneity; Sox2; SRR2
资金
- Canadian Institutes of Health Research (CIHR)
- Canadian Breast Cancer Foundation
- Izaak Walton Killam Memorial Scholarship
- CIHR Vanier Canada Graduate Scholarships
- Alberta Cancer Foundation Cancer Research Postdoctoral Fellowship
- Taibah University, Al Madina Al Munawarrah, Saudi Arabia
We have recently described a novel phenotypic dichotomy within estrogen receptor-positive breast cancer cells; the cell subset responsive to a Sox2 regulatory region (SRR2) reporter (RR cells) are significantly more tumorigenic than the reporter unresponsive (RU) cells. Here, we report that a similar phenomenon also exists in triple negative breast cancer (TNBC), with RR cells more tumorigenic than RU cells. First, examination of all 3 TNBC cell lines stably infected with the SRR2 reporter revealed the presence of a cell subset exhibiting reporter activity. Second, RU and RR cells purified by flow cytometry showed that RR cells expressed higher levels of CD44, generated more spheres in a limiting dilution mammosphere formation assay, and formed larger and more complex structures in Matrigel. Third, within the CD44(High)/CD24(-) tumor-initiating cell population derived from MDA-MB-231, RR cells were significantly more tumorigenic than RU cells in an in vivo SCID/Beige xenograft mouse model. Examination of 4 TNBC tumors from patients also revealed the presence of a RR cell subset, ranging from 1.1-3.8%. To conclude, we described a novel phenotypic heterogeneity within TNBC, and the SRR2 reporter responsiveness is a useful marker for identifying a highly tumorigenic cell subset within the CD44(High)/CD24(-) tumor-initiating cell population.
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