Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2023; 14:481-482.

Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer

Astrid Escudero-Esparza, Michael Bartoschek, Chrysostomi Gialeli, Marcin Okroj, Sioned Owen, Karin Jirström, Akira Orimo, Wen G. Jiang, Kristian Pietras and Anna M. Blom _

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Oncotarget. 2016; 7:76920-76933. https://doi.org/10.18632/oncotarget.12729

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Abstract

Astrid Escudero-Esparza1, Michael Bartoschek2,*, Chrysostomi Gialeli1,*, Marcin Okroj3, Sioned Owen4, Karin Jirström5, Akira Orimo6, Wen G. Jiang4, Kristian Pietras2, Anna M. Blom1

1Department of Translational Medicine, Lund University, Malmö, Sweden

2Department of Laboratory Medicine, Lund University, Lund, Sweden

3Department of Medical Biotechnology, Medical University of Gdańsk, Gdańsk, Poland

4Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, UK

5Department of Clinical Sciences, Lund University, Lund, Sweden

6Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan

*These authors contributed equally to this work

Correspondence to:

Anna M. Blom, email: [email protected]

Keywords: breast cancer, tumor suppressor, CSMD1, complement system, invasion

Received: June 15, 2016     Accepted: October 11, 2016     Published: October 18, 2016

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.


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