Oncotarget

Research Papers:

The dual role of asporin in breast cancer progression

Dana Simkova, Gvantsa Kharaishvili, Gabriela Korinkova, Tomas Ozdian, Tereza Suchánková-Kleplová, Tomas Soukup, Michal Krupka, Adela Galandakova, Petr Dzubak, Maria Janikova, Jiri Navratil, Zuzana Kahounova, Karel Soucek and Jan Bouchal _

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Oncotarget. 2016; 7:52045-52060. https://doi.org/10.18632/oncotarget.10471

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Abstract

Dana Simkova1, Gvantsa Kharaishvili1, Gabriela Korinkova1, Tomas Ozdian2, Tereza Suchánková-Kleplová3, Tomas Soukup3, Michal Krupka4, Adela Galandakova5, Petr Dzubak2, Maria Janikova1, Jiri Navratil6, Zuzana Kahounova7,8, Karel Soucek7,8,9, Jan Bouchal1

1Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

2Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

3Department of Histology and Embryology, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic

4Department of Immunology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

5Department of Medical Chemistry and Biochemistry, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

6Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic

7Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic

8Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic

9Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic

Correspondence to:

Jan Bouchal, email: jan.bouchal@upol.cz

Keywords: asporin, 3D cultivation, stiffness, grade, breast cancer

Received: October 14, 2015     Accepted: June 29, 2016     Published: July 7, 2016

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.


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