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CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells

Pancreatic cancer (PC) is one of the deadliest cancers and remains a major challenge due to its invasive and metastatic nature. Increased levels of CCR5 and CCL5 have established indicators for disease status in various cancers, including PC. However, their role in invasion and metastasis of PC is n...

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Autores principales: Singh, Santosh Kumar, Mishra, Manoj K., Eltoum, Isam-Eldin A., Bae, Sejong, Lillard, James W., Singh, Rajesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778036/
https://www.ncbi.nlm.nih.gov/pubmed/29358632
http://dx.doi.org/10.1038/s41598-018-19643-0
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author Singh, Santosh Kumar
Mishra, Manoj K.
Eltoum, Isam-Eldin A.
Bae, Sejong
Lillard, James W.
Singh, Rajesh
author_facet Singh, Santosh Kumar
Mishra, Manoj K.
Eltoum, Isam-Eldin A.
Bae, Sejong
Lillard, James W.
Singh, Rajesh
author_sort Singh, Santosh Kumar
collection PubMed
description Pancreatic cancer (PC) is one of the deadliest cancers and remains a major challenge due to its invasive and metastatic nature. Increased levels of CCR5 and CCL5 have established indicators for disease status in various cancers, including PC. However, their role in invasion and metastasis of PC is not known. Here we conducted immunohistochemistry of PC tissues and found elevated epithelial staining for CCR5 and CCL5 in metastatic PC tissues compared to non-neoplastic. In vitro experiments, such as flow cytometry, immunofluorescence and western blotting with human PC cell lines (AsPc-1, BxPc-3 and MIA PaCa-2), showed higher expression levels of CCR5. The CCL5 activation of PC cells expressing CCR5 increased their invasive potential, while treatment with CCR5 inhibitor maraviroc inhibited the CCL5 activation. CCL5 induced proliferation of PC cells was mediated through F-actin polymerization, while there was marked reduction when the cells were treated with maraviroc. The direct interaction of CCR5 with CCL5 was verified using a calcium mobilization assay. Taken together, our results demonstrate that CCR5 and CCL5 are potential markers for metastatic PC cancer, and their interaction leads to the increased PC cell invasion. Thus, blocking CCR5/CCL5 axis might prove beneficial to prevent metastasis and provide a more therapeutic strategy to control PC progression.
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spelling pubmed-57780362018-01-31 CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells Singh, Santosh Kumar Mishra, Manoj K. Eltoum, Isam-Eldin A. Bae, Sejong Lillard, James W. Singh, Rajesh Sci Rep Article Pancreatic cancer (PC) is one of the deadliest cancers and remains a major challenge due to its invasive and metastatic nature. Increased levels of CCR5 and CCL5 have established indicators for disease status in various cancers, including PC. However, their role in invasion and metastasis of PC is not known. Here we conducted immunohistochemistry of PC tissues and found elevated epithelial staining for CCR5 and CCL5 in metastatic PC tissues compared to non-neoplastic. In vitro experiments, such as flow cytometry, immunofluorescence and western blotting with human PC cell lines (AsPc-1, BxPc-3 and MIA PaCa-2), showed higher expression levels of CCR5. The CCL5 activation of PC cells expressing CCR5 increased their invasive potential, while treatment with CCR5 inhibitor maraviroc inhibited the CCL5 activation. CCL5 induced proliferation of PC cells was mediated through F-actin polymerization, while there was marked reduction when the cells were treated with maraviroc. The direct interaction of CCR5 with CCL5 was verified using a calcium mobilization assay. Taken together, our results demonstrate that CCR5 and CCL5 are potential markers for metastatic PC cancer, and their interaction leads to the increased PC cell invasion. Thus, blocking CCR5/CCL5 axis might prove beneficial to prevent metastasis and provide a more therapeutic strategy to control PC progression. Nature Publishing Group UK 2018-01-22 /pmc/articles/PMC5778036/ /pubmed/29358632 http://dx.doi.org/10.1038/s41598-018-19643-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Singh, Santosh Kumar
Mishra, Manoj K.
Eltoum, Isam-Eldin A.
Bae, Sejong
Lillard, James W.
Singh, Rajesh
CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells
title CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells
title_full CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells
title_fullStr CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells
title_full_unstemmed CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells
title_short CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells
title_sort ccr5/ccl5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778036/
https://www.ncbi.nlm.nih.gov/pubmed/29358632
http://dx.doi.org/10.1038/s41598-018-19643-0
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