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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...

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Autores principales: Roy, Ananya, Femel, Julia, Huijbers, Elisabeth J. M., Spillmann, Dorothe, Larsson, Erik, Ringvall, Maria, Olsson, Anna-Karin, Åbrink, Magnus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
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.
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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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