title: The chemokine receptor CCR7 promotes mammary tumorigenesis through amplification of stem-like cells.
abstract: The chemokine receptor CCR7 is widely implicated in breast cancer pathobiology. Although recent reports correlated high CCR7 levels with more advanced tumor grade and poor prognosis, limited in vivo data are available regarding its specific function in mammary gland neoplasia and the underlying mechanisms involved. To address these questions we generated a bigenic mouse model of breast cancer combined with CCR7 deletion, which revealed that CCR7 ablation results in a considerable delay in tumor onset as well as significantly reduced tumor burden. Importantly, CCR7 was found to exert its function by regulating mammary cancer stem-like cells in both murine and human tumors. In vivo experiments showed that loss of CCR7 activity either through deletion or pharmacological antagonism significantly decreased functional pools of stem-like cells in mouse primary mammary tumors, providing a mechanistic explanation for the tumor-promoting role of this chemokine receptor. These data characterize the oncogenic properties of CCR7 in mammary epithelial neoplasia and point to a new route for therapeutic intervention to target evasive cancer stem cells.
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: S T
authors.initials: ST
authors.lastname: Boyle
authors.affiliation: The Robinson Institute, University of Adelaide, Adelaide, South Australia, Australia.|Discipline of Surgery, School of Medicine, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: W V
authors.initials: WV
authors.lastname: Ingman
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Poltavets
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: J W
authors.initials: JW
authors.lastname: Faulkner
authors.affiliation: Breast, Endocrine and Surgical Oncology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.|School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: R J
authors.initials: RJ
authors.lastname: Whitfield
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.|Centre for Molecular Pathology, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: S R
authors.initials: SR
authors.lastname: McColl
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Kochetkova
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D054400:Receptors, CCR7 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
chemical_list: C515370:CCR7 protein, human; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7