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CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors

The interaction between cancer cells and molecular cues provided by tumor stromal cells plays a crucial role in cancer growth and progression. We have recently reported that the outcome of interaction between tumor cells and stromal cells is dependent on the gene expression signature of tumor cells....

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Autores principales: Al-toub, Mashael, Almohawes, Mohammad, Vishnubalaji, Radhakrishnan, Alfayez, Musaad, Aldahmash, Abdullah, Kassem, Moustapha, Alajez, Nehad M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459874/
https://www.ncbi.nlm.nih.gov/pubmed/30993013
http://dx.doi.org/10.1038/s41420-019-0169-3
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author Al-toub, Mashael
Almohawes, Mohammad
Vishnubalaji, Radhakrishnan
Alfayez, Musaad
Aldahmash, Abdullah
Kassem, Moustapha
Alajez, Nehad M.
author_facet Al-toub, Mashael
Almohawes, Mohammad
Vishnubalaji, Radhakrishnan
Alfayez, Musaad
Aldahmash, Abdullah
Kassem, Moustapha
Alajez, Nehad M.
author_sort Al-toub, Mashael
collection PubMed
description The interaction between cancer cells and molecular cues provided by tumor stromal cells plays a crucial role in cancer growth and progression. We have recently reported that the outcome of interaction between tumor cells and stromal cells is dependent on the gene expression signature of tumor cells. In the current study, we observed that several cancer cell lines, e.g., MCF7 breast cancer line, exhibited growth advantage when cultured in the presence of conditioned media (CM) derived from human bone marrow stromal stem cells (hBMSCs). Regarding the underlying molecular mechanism, we have identified CXCR7 as highly expressed by MCF7 cells and that it mediated the enhanced growth in response to hBMSC CM. Regarding the clinical relevance, we found an inverse correlation between the level of tumor gene expression of CXCR7 in bladder, breast, cervical, kidney, liver, lung, pancreatic, stomach, and uterine cancers, and patients’ overall survival. Interestingly, significant positive correlation between CXCR7 and CXCL12 gene expression (Pearson = 0.3, p = 2.0 × 10(–16)) was observed in breast cancer patients, suggesting a biological role for the CXCR7/CXCL12 genetic circuit in breast cancer biology. Our data provide insight into the molecular mechanisms by which stromal-derived microenvironmental cues mediate CXCR7 signaling and growth enhancement of breast cancer cells. Therapeutic targeting of this circuit might provide novel therapeutic opportunity for breast cancer.
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spelling pubmed-64598742019-04-16 CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors Al-toub, Mashael Almohawes, Mohammad Vishnubalaji, Radhakrishnan Alfayez, Musaad Aldahmash, Abdullah Kassem, Moustapha Alajez, Nehad M. Cell Death Discov Article The interaction between cancer cells and molecular cues provided by tumor stromal cells plays a crucial role in cancer growth and progression. We have recently reported that the outcome of interaction between tumor cells and stromal cells is dependent on the gene expression signature of tumor cells. In the current study, we observed that several cancer cell lines, e.g., MCF7 breast cancer line, exhibited growth advantage when cultured in the presence of conditioned media (CM) derived from human bone marrow stromal stem cells (hBMSCs). Regarding the underlying molecular mechanism, we have identified CXCR7 as highly expressed by MCF7 cells and that it mediated the enhanced growth in response to hBMSC CM. Regarding the clinical relevance, we found an inverse correlation between the level of tumor gene expression of CXCR7 in bladder, breast, cervical, kidney, liver, lung, pancreatic, stomach, and uterine cancers, and patients’ overall survival. Interestingly, significant positive correlation between CXCR7 and CXCL12 gene expression (Pearson = 0.3, p = 2.0 × 10(–16)) was observed in breast cancer patients, suggesting a biological role for the CXCR7/CXCL12 genetic circuit in breast cancer biology. Our data provide insight into the molecular mechanisms by which stromal-derived microenvironmental cues mediate CXCR7 signaling and growth enhancement of breast cancer cells. Therapeutic targeting of this circuit might provide novel therapeutic opportunity for breast cancer. Nature Publishing Group UK 2019-04-11 /pmc/articles/PMC6459874/ /pubmed/30993013 http://dx.doi.org/10.1038/s41420-019-0169-3 Text en © The Author(s) 2019 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
Al-toub, Mashael
Almohawes, Mohammad
Vishnubalaji, Radhakrishnan
Alfayez, Musaad
Aldahmash, Abdullah
Kassem, Moustapha
Alajez, Nehad M.
CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors
title CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors
title_full CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors
title_fullStr CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors
title_full_unstemmed CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors
title_short CXCR7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors
title_sort cxcr7 signaling promotes breast cancer survival in response to mesenchymal stromal stem cell-derived factors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459874/
https://www.ncbi.nlm.nih.gov/pubmed/30993013
http://dx.doi.org/10.1038/s41420-019-0169-3
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