Oncotarget

Research Papers:

Triple negative breast cancers comprise a highly tumorigenic cell subpopulation detectable by its high responsiveness to a Sox2 regulatory region 2 (SRR2) reporter

Karen Jung, Nidhi Gupta, Peng Wang, Jamie T. Lewis, Keshav Gopal, Fang Wu, Xiaoxia Ye, Abdulraheem Alshareef, Bassam S. Abdulkarim, Donna N. Douglas, Norman M. Kneteman and Raymond Lai _

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Oncotarget. 2015; 6:10366-10373. https://doi.org/10.18632/oncotarget.3590

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Abstract

Karen Jung1,*, Nidhi Gupta2,*, Peng Wang2, Jamie T. Lewis3, Keshav Gopal2, Fang Wu2, Xiaoxia Ye2, Abdulraheem Alshareef2, Bassam S. Abdulkarim4, Donna N. Douglas3, Norman M. Kneteman3 and Raymond Lai1,2,5

1 Department of Oncology, University of Alberta, Edmonton, Alberta, Canada

2 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada

3 Department of Surgery, University of Alberta, Edmonton, Alberta, Canada

4 Department of Oncology, McGill University, Montreal, Quebec, Canada

5 DynaLIFEDx Medical Laboratories, Edmonton, Alberta, Canada

* These authors are Co-first authors

Correspondence to:

Raymond Lai, email:

Keywords: breast cancer, tumour cell heterogeneity, Sox2, SRR2

Received: January 21, 2015 Accepted: February 17, 2015 Published: April 30, 2015

Abstract

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 CD44High/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 CD44High/CD24-tumor-initiating cell population.


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