title: The dual role of asporin in breast cancer progression.
abstract: Asporin has been reported as a tumor suppressor in breast cancer, while asporin-activated invasion has been described in gastric cancer. According to our in silico search, high asporin expresion associates with significantly better relapse free survival (RFS) in patients with low-grade tumors but RFS is significantly worse in patients with grade 3 tumors. In line with other studies, we have confirmed asporin expression by RNA scope in situ hybridization in cancer associated fibroblasts. We have also found asporin expression in the Hs578T breast cancer cell line which we confirmed by quantitative RT-PCR and western blotting. From multiple testing, we found that asporin can be downregulated by bone morphogenetic protein 4 while upregulation may be facilited by serum-free cultivation or by three dimensional growth in stiff Alvetex scaffold. Downregulation by shRNA inhibited invasion of Hs578T as well as of CAFs and T47D cells. Invasion of asporin-negative MDA-MB-231 and BT549 breast cancer cells through collagen type I was enhanced by recombinant asporin. Besides other investigations, large scale analysis of aspartic acid repeat polymorphism will be needed for clarification of the asporin dual role in progression of breast cancer.
authors.affiliation: Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Simkova
authors.affiliation: Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Gvantsa
authors.initials: G
authors.lastname: Kharaishvili
authors.affiliation: Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Korinkova
authors.affiliation: Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Ozdian
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Suchánková-Kleplová
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Soukup
authors.affiliation: Department of Immunology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Krupka
authors.affiliation: Department of Medical Chemistry and Biochemistry, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Adela
authors.initials: A
authors.lastname: Galandakova
authors.affiliation: Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Dzubak
authors.affiliation: Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Maria
authors.initials: M
authors.lastname: Janikova
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Navratil
authors.affiliation: Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic.|Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kahounova
authors.affiliation: Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic.|Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.|Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Soucek
authors.affiliation: Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Bouchal
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: C439889:ASPN protein, human; D016326:Extracellular Matrix Proteins
keywords: 3D cultivation; asporin; breast cancer; grade; stiffness