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Cancer cell CCL5 mediates bone marrow independent angiogenesis in breast cancer

Sax, Michael John, Gasch, Christin, Athota, Vineel Rag, Freeman, Ruth, Rasighaemi, Parisa, Westcott, David Elton, Day, Christopher John, Nikolic, Iva, Elsworth, Benjamin, Wei, Ming, Rogers, Kelly, Swarbrick, Alexander, Mittal, Vivek, Pouliot, Normand and Mellick, Albert Sleiman 2016, Cancer cell CCL5 mediates bone marrow independent angiogenesis in breast cancer, Oncotarget, vol. 7, no. 51, pp. 85437-85449, doi: 10.18632/oncotarget.13387.

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Title Cancer cell CCL5 mediates bone marrow independent angiogenesis in breast cancer
Author(s) Sax, Michael John
Gasch, Christin
Athota, Vineel Rag
Freeman, Ruth
Rasighaemi, Parisa
Westcott, David Elton
Day, Christopher John
Nikolic, Iva
Elsworth, Benjamin
Wei, Ming
Rogers, Kelly
Swarbrick, Alexander
Mittal, Vivek
Pouliot, Normand
Mellick, Albert Sleiman
Journal name Oncotarget
Volume number 7
Issue number 51
Start page 85437
End page 85449
Total pages 13
Publisher Impact Journals
Place of publication Albany, N.Y.
Publication date 2016-12-20
ISSN 1949-2553
Keyword(s) CCL5
CCR5
angiogenesis
breast cancer
shRNAi
Summary It has recently been suggested that the chemokine receptor (CCR5) is required for bone marrow (BM) derived endothelial progenitor cell (EPC) mediated angiogenesis. Here we show that suppression of either cancer cell produced CCL5, or host CCR5 leads to distinctive vascular and tumor growth defects in breast cancer. Surprisingly, CCR5 restoration in the BM alone was not sufficient to rescue the wild type phenotype, suggesting that impaired tumor growth associated with inhibiting CCL5/CCR5 is not due to defects in EPC biology. Instead, to promote angiogenesis cancer cell CCL5 may signal directly to endothelium in the tumor-stroma. In support of this hypothesis, we have also shown: (i) that endothelial cell CCR5 levels increases in response to tumor-conditioned media; (ii) that the amount of CCR5+ tumor vasculature correlates with invasive grade; and (iii) that inhibition of CCL5/CCR5 signaling impairs endothelial cell migration, associated with a decrease in activation of mTOR/AKT pathway members. Finally, we show that treatment with CCR5 antagonist results in less vasculature, impaired tumor growth, reduced metastases and improved survival. Taken as a whole, this work demonstrates that directly inhibiting CCR5 expressing vasculature constitutes a novel strategy for inhibiting angiogenesis and blocking metastatic progression in breast cancer.
Language eng
DOI 10.18632/oncotarget.13387
Field of Research 111299 Oncology and Carcinogenesis not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30096304

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.