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Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma
In hematopoietic cells, serglycin proteoglycans mainly contribute to proper storage and secretion of inflammatory mediators via their negatively charged glycosaminoglycans. Serglycin proteoglycans are also expressed in cancer cells where increased expression has been linked to poor prognosis. Howeve...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880347/ https://www.ncbi.nlm.nih.gov/pubmed/27223472 http://dx.doi.org/10.1371/journal.pone.0156151 |
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author | Roy, Ananya Femel, Julia Huijbers, Elisabeth J. M. Spillmann, Dorothe Larsson, Erik Ringvall, Maria Olsson, Anna-Karin Åbrink, Magnus |
author_facet | Roy, Ananya Femel, Julia Huijbers, Elisabeth J. M. Spillmann, Dorothe Larsson, Erik Ringvall, Maria Olsson, Anna-Karin Åbrink, Magnus |
author_sort | Roy, Ananya |
collection | PubMed |
description | In hematopoietic cells, serglycin proteoglycans mainly contribute to proper storage and secretion of inflammatory mediators via their negatively charged glycosaminoglycans. Serglycin proteoglycans are also expressed in cancer cells where increased expression has been linked to poor prognosis. However, the serglycin-dependent mediators promoting cancer progression remain to be determined. In the present study we report that genetic ablation of serglycin proteoglycan completely blocks lung metastasis in the MMTV-PyMT-driven mouse breast cancer model, while serglycin-deficiency did not affect primary tumour growth or number of mammary tumours. Although E-cadherin expression was higher in the serglycin-deficient primary tumour tissue, indicating reduced invasiveness, serglycin-deficient tumour cells were still detected in the circulation. These data suggest that serglycin proteoglycans play a role in extravasation as well as colonization and growth of metastatic cells. A microarray expression analysis and functional annotation of differentially expressed genes identified several biological pathways where serglycin may be important. Our results suggest that serglycin and serglycin-dependent mediators are potential drug targets to prevent metastatic disease/dissemination of cancer. |
format | Online Article Text |
id | pubmed-4880347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48803472016-06-09 Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma Roy, Ananya Femel, Julia Huijbers, Elisabeth J. M. Spillmann, Dorothe Larsson, Erik Ringvall, Maria Olsson, Anna-Karin Åbrink, Magnus PLoS One Research Article In hematopoietic cells, serglycin proteoglycans mainly contribute to proper storage and secretion of inflammatory mediators via their negatively charged glycosaminoglycans. Serglycin proteoglycans are also expressed in cancer cells where increased expression has been linked to poor prognosis. However, the serglycin-dependent mediators promoting cancer progression remain to be determined. In the present study we report that genetic ablation of serglycin proteoglycan completely blocks lung metastasis in the MMTV-PyMT-driven mouse breast cancer model, while serglycin-deficiency did not affect primary tumour growth or number of mammary tumours. Although E-cadherin expression was higher in the serglycin-deficient primary tumour tissue, indicating reduced invasiveness, serglycin-deficient tumour cells were still detected in the circulation. These data suggest that serglycin proteoglycans play a role in extravasation as well as colonization and growth of metastatic cells. A microarray expression analysis and functional annotation of differentially expressed genes identified several biological pathways where serglycin may be important. Our results suggest that serglycin and serglycin-dependent mediators are potential drug targets to prevent metastatic disease/dissemination of cancer. Public Library of Science 2016-05-25 /pmc/articles/PMC4880347/ /pubmed/27223472 http://dx.doi.org/10.1371/journal.pone.0156151 Text en © 2016 Roy et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Roy, Ananya Femel, Julia Huijbers, Elisabeth J. M. Spillmann, Dorothe Larsson, Erik Ringvall, Maria Olsson, Anna-Karin Åbrink, Magnus Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma |
title | Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma |
title_full | Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma |
title_fullStr | Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma |
title_full_unstemmed | Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma |
title_short | Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma |
title_sort | targeting serglycin prevents metastasis in murine mammary carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880347/ https://www.ncbi.nlm.nih.gov/pubmed/27223472 http://dx.doi.org/10.1371/journal.pone.0156151 |
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