Heparanase regulates esophageal keratinocyte differentiation through nuclear translocation and heparan sulfate cleavage
| Autor: | Noriaki Tanaka, Tetsuji Nobuhisa, Yoshio Naomoto, Motowo Nakajima, Anil K. Rustgi, Takaomi Okawa, Hiroshi Nakagawa, Yasuhiro Shirakawa, Junji Matsuoka, Takaaki Mizushima, Tomoki Yamatsuji, Hironori Matsuura, Masahiko Kobayashi, Munenori Takaoka |
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| Rok vydání: | 2006 |
| Předmět: |
Keratinocytes
Cancer Research Cellular differentiation Blotting Western Cell Biology Extracellular matrix chemistry.chemical_compound Esophagus Proliferating Cell Nuclear Antigen medicine Humans Heparanase Protein Precursors Molecular Biology Involucrin Glucuronidase Cell Nucleus Cell Differentiation Cell Biology Heparan sulfate Immunohistochemistry Molecular biology Cell nucleus medicine.anatomical_structure chemistry Cytoplasm Heparitin Sulfate Developmental Biology |
| Zdroj: | Differentiation. 74:235-243 |
| ISSN: | 0301-4681 |
| Popis: | Heparanase is an endo-beta-glucuronidase that specifically cleaves heparan sulfate (HS) chains. Heparanase is involved in the process of metastasis and angiogenesis through the degradation of HS chains of the extracellular matrix and cell surface. Recently, we demonstrated that heparanase was localized in the cell nucleus of normal esophageal epithelium and esophageal cancer, and that its expression was correlated with cell differentiation. However, the nuclear function of heparanase remains unknown. To elucidate the role of heparanase in esophageal epithelial differentiation, primary human esophageal cells were grown in monolayer as well as organotypic cultures, and cell differentiation was induced. Expression of heparanase, HS, involucrin, and p27 was determined by immunostaining and Western blotting. SF4, a novel pharmacological inhibitor, was used to specifically inhibit heparanase activity. Upon esophageal cell differentiation, heparanase was translocated from the cytoplasm to the nucleus. Such translocation of heparanase appeared to be associated with the degradation of HS chains in the nucleus and changes in the expression of keratinocyte differentiation markers such as p27 and involucrin, whose induction was inhibited by SF4. Furthermore, these in vitro observations agreed with the expression pattern of heparanase, HS, involucrin, cytokeratin 13, and p27 in normal esophageal epithelium. Nuclear translocation of heparanase and its catalytic cleavage of HS may play a critical role in the differentiation of esophageal epithelial cells. Our study provides a novel insight into the role of heparanase in an essential differentiation process. |
| Databáze: | OpenAIRE |
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