Heterogeneous Expression of Claudin-4 in Human Colorectal Cancer: Decreased Claudin-4 Expression at the Invasive Front Correlates Cancer Invasion and Metastasis
| Autor: | Yasushi Seo, Hideki Chiba, Hiroshi Yokozaki, Shuho Semba, Norimasa Sawada, Masato Kasuga, Junya Ueda |
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| Rok vydání: | 2007 |
| Předmět: |
Small interfering RNA
Pathology medicine.medical_specialty endocrine system diseases Colorectal cancer Blotting Western Biology urologic and male genital diseases digestive system Pathology and Forensic Medicine Metastasis Cell Movement medicine Humans Neoplasm Invasiveness Claudin-4 Neoplasm Metastasis RNA Small Interfering Claudin Molecular Biology Gene knockdown Membrane Proteins Cancer Cell Biology General Medicine medicine.disease Immunohistochemistry digestive system diseases Cancer cell Cancer research Neoplasm Recurrence Local Colorectal Neoplasms tissues |
| Zdroj: | Pathobiology. 74:32-41 |
| ISSN: | 1423-0291 1015-2008 |
| DOI: | 10.1159/000101049 |
| Popis: | Objective: Claudin-4 plays a key role in constructing the tight junction (TJ), and altered claudin-4 expression has been documented in various human malignancies; however, little is known about the biological significance of claudin-4 in colorectal cancers (CRCs). The aim of this study is to investigate the significance of claudin-4 expression in CRC and its association with clinicopathological factors. Methods: The levels of claudin-4 expression in a total of 129 CRCs and 44 metastatic tumors were examined by immunohistochemistry. A small interfering RNA (siRNA)-mediated claudin-4 knockdown examination was also conducted to assess the biological role(s) of claudin-4 in cultured cells. Results: Expression of claudin-4 at the intercellular membrane was well preserved at the surface of the tumor; however, decreased claudin-4 expression was detected in 57% of CRCs, particularly at the invasive front. Interestingly, decreased claudin-4 expression was detected in metastatic lesions of CRC. The siRNA-mediated claudin-4 knockdown in SW480 claudin-4-positive CRC cells upregulated cell motility, whereas no significant change was detected in cell proliferation. Conclusions: These observations suggested that disruption of claudin-4-mediated TJ construction enhances cancer cell invasion and metastasis in human CRC. Claudin-4 might be a good biomarker for diagnosing the risk of distant metastasis. |
| Databáze: | OpenAIRE |
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