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Tumour Biol. 2016 Oct;37(10):13425-13433. Epub 2016 Jul 27.

Downregulation of CXCR7 inhibits proliferative capacity and stem cell-like properties in breast cancer stem cells.

Author information

1
Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University, 5 Tongxiang Road, Mudanjiang, Heilongjiang, 157011, China.
2
Department of Medical Ultrasonics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, China.
3
Department of Orthopaedic Surgery, Mudanjiang Forestry Central Hospital, Mudanjiang, Heilongjiang, 157000, China.
4
Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University, 5 Tongxiang Road, Mudanjiang, Heilongjiang, 157011, China. caijuanli123@163.com.

Abstract

Breast cancer stem cells (bCSCs) are considered an obstacle in breast cancer therapy because they exhibit long-term proliferative potential, phenotypic plasticity and high resistance to the current therapeutics. CXC chemokine receptor type 7 (CXCR7), which provides a growth advantage to breast cancer cells, has recently been demonstrated to play an important role in the maintenance of stem cell-like properties in the CSCs of glioblastoma and lung cancer, yet its role in bCSCs remains elusive. In this study, CD44+/CD24low bCSC-enriched cells (bCSCs for short) were isolated from MCF-7 cells, and CXCR7 was stably knocked down in bCSCs via lentivirus-mediated transduction with CXCR7 short hairpin RNA (shRNA). Knockdown of CXCR7 in bCSCs decreased the proportion of CD44+/CD24low cells, and markedly reduced the clonogenicity of the cells. Moreover, silencing of CXCR7 downregulated the expression of stem cell markers, such as aldehyde dehydrogenase 1 (ALDH1), Oct4, and Nanog. In addition, CXCR7 silencing in bCSCs suppressed cell proliferation and G1/S transition in vitro, and delayed tumor growth in vivo in a xenograft mouse model. In situ immunohistochemical analysis revealed a reduction in Ki-67 expression and enhanced apoptosis in the xenograft tumors as a result of CXCR7 silencing. Furthermore, combined treatment with CXCR7 silencing and epirubicin displayed an outstanding anti-tumor effect compared with either single treatment. Our study demonstrates that CXCR7 plays a critical role in the maintenance of stem cell-like properties and promotion of growth in bCSCs, and suggests that CXCR7 may be a candidate target for bCSCs in breast cancer therapy.

KEYWORDS:

Breast cancer stem cell; CXCR7; Epirubicin; Proliferation; Tumorigenicity

PMID:
27460092
DOI:
10.1007/s13277-016-5180-1
[Indexed for MEDLINE]

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