title: Triple negative breast cancers comprise a highly tumorigenic cell subpopulation detectable by its high responsiveness to a Sox2 regulatory region 2 (SRR2) reporter.
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 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.
authors: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors: Karen
authors: K
authors: Jung
authors: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors: Nidhi
authors: N
authors: Gupta
authors: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors: Peng
authors: P
authors: Wang
authors: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors: Jamie T
authors: JT
authors: Lewis
authors: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors: Keshav
authors: K
authors: Gopal
authors: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors: Fang
authors: F
authors: Wu
authors: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors: Xiaoxia
authors: X
authors: Ye
authors: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors: Abdulraheem
authors: A
authors: Alshareef
authors: Department of Oncology, McGill University, Montreal, Quebec, Canada.
authors: Bassam S
authors: BS
authors: Abdulkarim
authors: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors: Donna N
authors: DN
authors: Douglas
authors: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors: Norman M
authors: NM
authors: Kneteman
authors: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.|Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.|DynaLIFE Dx Medical Laboratories, Edmonton, Alberta, Canada.
authors: Raymond
authors: R
authors: Lai
mesh_terms: D000818:Animals; D051927:CD24 Antigen / Q000096:biosynthesis; D045744:Cell Line, Tumor; D005260:Female; D064593:Heterografts; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012045:Regulatory Sequences, Nucleic Acid; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: SRR2; Sox2; breast cancer; tumour cell heterogeneity