title: Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer.
abstract: Human CUB and Sushi multiple domains 1 (CSMD1) is a membrane-bound complement inhibitor suggested to act as a putative tumor suppressor gene, since allelic loss of this region encompassing 8p23 including CSMD1 characterizes various malignancies. Here, we assessed the role of CSMD1 as a tumor suppressor gene in the development of breast cancer in vitro and in vivo. We found that human breast tumor tissues expressed CSMD1 at lower levels compared to that in normal mammary tissues. The decreased expression of CSMD1 was linked to a shorter overall survival of breast cancer patients. We also revealed that expression of CSMD1 in human breast cancer cells BT-20 and MDA-MB-231 significantly inhibited their malignant phenotypes, including migration, adhesion and invasion. Conversely, stable silencing of CSMD1 expression in T47D cells enhanced cancer cell migratory, adherent and clonogenic abilities. Moreover, expression of CSMD1 in the highly invasive MDA-MB-231 cells diminished their signaling potential as well as their stem cell-like properties as assessed by measurement of aldehyde dehydrogenase activity. In a xenograft model, expression of CSMD1 blocked the ability of cancer cells to metastasize to secondary sites in vivo, likely via inhibiting local invasion but not the extravasation into distant tissues. Taken together, these findings demonstrate the role of CSMD1 as a tumor suppressor gene in breast cancer.
authors.affiliation: Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Astrid
authors.initials: A
authors.lastname: Escudero-Esparza
authors.affiliation: Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Bartoschek
authors.affiliation: Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Chrysostomi
authors.initials: C
authors.lastname: Gialeli
authors.affiliation: Department of Medical Biotechnology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Okroj
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Sioned
authors.initials: S
authors.lastname: Owen
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Orimo
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Kristian
authors.initials: K
authors.lastname: Pietras
authors.affiliation: Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011379:Prognosis; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins
chemical_list: C477880:CSMD1 protein, human; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins
keywords: CSMD1; breast cancer; complement system; invasion; tumor suppressor