title: Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma.
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.
authors.affiliation: Swedish University of Agricultural Sciences, Department of Biomedical Sciences and Veterinary Public Health, Box 7028, 75007, Uppsala, Sweden.|Uppsala University, Department of Medical Biochemistry and Microbiology, Box 582, 75123, Uppsala, Sweden.
authors.forename: Ananya
authors.initials: A
authors.lastname: Roy
authors.affiliation: Uppsala University, Department of Medical Biochemistry and Microbiology, Box 582, 75123, Uppsala, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Femel
authors.affiliation: VUMC-Cancer Center Amsterdam, Angiogenesis Laboratory, Dept. of Medical Oncology, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Elisabeth J M
authors.initials: EJ
authors.lastname: Huijbers
authors.affiliation: Uppsala University, Department of Medical Biochemistry and Microbiology, Box 582, 75123, Uppsala, Sweden.
authors.forename: Dorothe
authors.initials: D
authors.lastname: Spillmann
authors.affiliation: Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck laboratory, 751 85, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Larsson
authors.affiliation: Uppsala University, Department of Medical Biochemistry and Microbiology, Box 582, 75123, Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Ringvall
authors.affiliation: Uppsala University, Department of Medical Biochemistry and Microbiology, Box 582, 75123, Uppsala, Sweden.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Olsson
authors.affiliation: Swedish University of Agricultural Sciences, Department of Biomedical Sciences and Veterinary Public Health, Box 7028, 75007, Uppsala, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Åbrink
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015820:Cadherins; C000611838:Cdh1 protein, mouse; D011509:Proteoglycans; D033921:Vesicular Transport Proteins; C075430:serglycin