Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model

Miao, J., Mu, D., Ergel, B., Singavarapu, R., Duan, Z., Powers, S., Oliva, E., Orsulic, S. (November 2008) Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model. Int J Cancer, 123 (9). pp. 2041-7.

URL: http://www.ncbi.nlm.nih.gov/pubmed/18726901
DOI: 10.1002/ijc.23726

Abstract

Hepsin is a serine protease that is widely expressed in different tissues and cell types, most prominently in the normal liver and kidney. Overexpression of hepsin has been associated with prostate cancers, ovarian cancers and renal cell carcinomas. The physiological functions of hepsin in normal tissues and tumors are poorly understood. To gain insight into its function in ovarian cancer, we analyzed the expression and subcellular localization of hepsin protein in ovarian cancer cell lines and tumors. We showed that the membrane-associated hepsin protein is present at desmosomal junctions, where it colocalizes with its putative proteolytic substrate hepatocyte growth factor. Consistent with the growing evidence that desmosomal junctions and their constituents play a role in cancer progression, we demonstrated that overexpression of hepsin promotes ovarian tumor growth in a mouse model. The ability of ectopic hepsin to induce tumor growth in mice is abrogated by the mutation of 3 critical residues in the catalytic domain, thus implicating the enzymatic activity of hepsin in promoting tumor progression.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Line, Tumor Cell Proliferation Desmosomes/*chemistry Disease Models, Animal Disease Progression Female Hepatocyte Growth Factor/analysis/physiology Humans Mice Mice, Inbred C57BL Mice, Nude Ovarian Neoplasms/*pathology Serine Endopeptidases/analysis/*physiology
Subjects: diseases & disorders > cancer
diseases & disorders
organism description > animal
organism description > animal > mammal > rodent > mouse
diseases & disorders > cancer > cancer types > ovarian cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Powers lab
Depositing User: Matt Covey
Date: 1 November 2008
Date Deposited: 26 Feb 2013 20:26
Last Modified: 26 Feb 2013 20:26
PMCID: PMC2653430
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27541

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