Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model
| Autor: | David Mu, Scott Powers, Burce Ergel, Rajasekhar Singavarapu, Sandra Orsulic, Jiangyong Miao, Esther Oliva, Zhenfeng Duan |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Hepsin Mice Nude Biology medicine.disease_cause Article Ovarian tumor Mice Cell Line Tumor medicine Animals Humans Cell Proliferation Ovarian Neoplasms Cell growth Hepatocyte Growth Factor Serine Endopeptidases Cancer Desmosomes medicine.disease Mice Inbred C57BL Disease Models Animal Oncology Tumor progression Serine Protease Hepsin Cancer research Disease Progression Female Carcinogenesis Ovarian cancer |
| Zdroj: | International journal of cancer. 123(9) |
| ISSN: | 1097-0215 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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