The chemokine receptor CCR7 promotes mammary tumorigenesis through amplification of stem-like cells

Oncogene
S T BoyleM Kochetkova

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.Oncogene advance online publication, 16 March 2015; doi:10.1038/onc.2015.66.

References

Apr 26, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S SharmaS M Dubinett
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
Apr 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wolfgang WeningerUlrich H von Andrian
May 21, 2003·Genes & Development·Gabriela DontuMax S Wicha
Jul 3, 2004·The Journal of Biological Chemistry·Katherine R PilkingtonShaun R McColl
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elise LavergneBehazine Combadiere
Aug 24, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Neslihan CabiogluAysegul Sahin
Apr 22, 2006·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F AndreM Cristofanilli
Oct 23, 2008·Cell Stem Cell·Toula BourasJane E Visvader
Jan 13, 2009·Cell Death and Differentiation·M KochetkovaS R McColl
Jul 9, 2010·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Jiang LiGuobin Wang
Dec 15, 2010·Translational Oncology·Heather D CunninghamCharlotte M Vines
May 10, 2011·Cell Stem Cell·Erika PastranaFiona Doetsch
Oct 13, 2011·The Journal of Pathology·Frances R Balkwill
Jan 10, 2012·Breast Cancer Research : BCR·Luciana P SchwabTiffany N Seagroves
May 31, 2012·Journal of Mammary Gland Biology and Neoplasia·Matthew J SmalleyJohn Stingl
Jun 1, 2012·Nature·Amy Maxmen
Jun 19, 2012·Cell Stem Cell·Jane E Visvader, Geoffrey J Lindeman
Aug 11, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jun MaStewart Sell
Apr 4, 2013·Nature Cell Biology·Jan Paul Medema
Apr 9, 2013·Molecular and Cellular Endocrinology·Andrew R Chin, Shizhen Emily Wang
Jun 27, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A GiordanoJ M Reuben
Dec 18, 2013·Breast Cancer Research and Treatment·Subir BiswasArindam Bhattacharyya
Aug 15, 2014·Developmental Cell·Jay S DesgrosellierDavid A Cheresh

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Citations

Jul 20, 2016·Cancer Treatment Reviews·A CarneroM E LLeonart
Sep 11, 2016·Pharmacology & Therapeutics·K-S N AtretkhanyD V Kuprash
Feb 1, 2017·Molecular Cancer·Sarah T BoyleMarina Kochetkova
Jan 30, 2018·Cellular & Molecular Immunology·Keqiang ChenJi Ming Wang
Jul 15, 2018·Cancer Science·Xueting Hu, Jincai Luo
Apr 15, 2020·The Journal of Experimental Medicine·Carly E WhyteShaun R McColl
Dec 30, 2017·Molecular and Clinical Oncology·Hyewon RyuHyo Jin Lee
Jul 23, 2018·Acta Biochimica Et Biophysica Sinica·Jiao WuRunxiang Yang
Dec 12, 2019·Journal of Cellular Biochemistry·Shiyi LiuYanxiang Cheng
Aug 19, 2017·Scientific Reports·Daichi KobayashiHaruko Hayasaka
Oct 21, 2020·International Journal of Molecular Sciences·Jan KorbeckiIrena Baranowska-Bosiacka
Apr 2, 2018·Current Opinion in Immunology·Qiaoli MaMichael Detmar

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