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Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Box 7028, S-75007 Uppsala, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
VUMC Canc Ctr Amsterdam, Dept Med Oncol, Angiogenesis Lab, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, e0156151Article in journal (Refereed) Published
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Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 11, no 5, e0156151
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Cancer and Oncology
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URN: urn:nbn:se:uu:diva-298897DOI: 10.1371/journal.pone.0156151ISI: 000376881700066PubMedID: 27223472OAI: oai:DiVA.org:uu-298897DiVA: diva2:948523
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Swedish Research Council, 2011-3533
Available from: 2016-07-12 Created: 2016-07-12 Last updated: 2017-11-28Bibliographically approved

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Roy, AnanyaSpillmann, DorotheLarsson, ErikRingvall, MariaOlsson, Anna-Karin
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Neuro-OncologyDepartment of Medical Biochemistry and MicrobiologyDepartment of Immunology, Genetics and Pathology
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