title: Downregulation of CXCR7 inhibits proliferative capacity and stem cell-like properties in breast cancer stem cells.
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+/CD24lowbCSC-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+/CD24lowcells, 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.
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University, 5 Tongxiang Road, Mudanjiang, Heilongjiang, 157011, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Medical Ultrasonics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Mudanjiang Forestry Central Hospital, Mudanjiang, Heilongjiang, 157000, China.
authors.forename: Zitao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University, 5 Tongxiang Road, Mudanjiang, Heilongjiang, 157011, China.
authors.forename: Yunshuang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University, 5 Tongxiang Road, Mudanjiang, Heilongjiang, 157011, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University, 5 Tongxiang Road, Mudanjiang, Heilongjiang, 157011, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University, 5 Tongxiang Road, Mudanjiang, Heilongjiang, 157011, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University, 5 Tongxiang Road, Mudanjiang, Heilongjiang, 157011, China. caijuanli123@163.com.
authors.forename: Caijuan
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C501896:ACKR3 protein, human; D012333:RNA, Messenger; D054387:Receptors, CXCR
keywords: Breast cancer stem cell; CXCR7; Epirubicin; Proliferation; Tumorigenicity