Abstract

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.

Keywords

cancer metastasis

Published in

PLoS ONE
2016, Volume: 11, number: 5, article number: e0156151
Publisher: PUBLIC LIBRARY SCIENCE

SLU Authors

• Roy, Ananya

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • Uppsala University

• Åbrink, Magnus

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

Sustainable Development Goals

Ensure healthy lives and promote well-being for all at all ages


UKÄ Subject classification

Cancer and Oncology


Publication identifier

DOI: https://doi.org/10.1371/journal.pone.0156151

Permanent link to this page (URI)

https://res.slu.se/id/publ/79432