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. Attached Files Name Description MIMEType Size Downloads gasch-cancercell-2016.pdf Published version application/pdf 1.77MB 15 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 Persistent URL http://hdl.handle.net/10536/DRO/DU:30096304 Document type: Journal Article Collections: School of Medicine Open Access Collection Related Links Link Description Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. 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. Versions Version Filter Type Tue, 16 May 2017, 15:09:12 EST Wed, 17 May 2017, 05:04:39 EST Wed, 17 May 2017, 06:08:05 EST Fri, 07 Jul 2017, 09:10:09 EST Fri, 07 Jul 2017, 09:15:10 EST Fri, 14 Jul 2017, 11:53:10 EST Fri, 07 Sep 2018, 12:39:44 EST Filtered Full Citation counts:   Cited 2 times in TR Web of Science Cited 3 times in Scopus Search Google Scholar Access Statistics: 141 Abstract Views, 16 File Downloads  -  Detailed Statistics Created: Tue, 16 May 2017, 15:09:12 EST

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.