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Down-Regulation of Claudin-3 Is Associated with Proliferative Potential in Early Gastric Cancers

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Abstract

Background

Claudins are tight junction (TJ) proteins, and the relationship between the level of expression and localization of TJ protein, and tumor aggressiveness in early gastric cancer (GC) is still far from clear.

Aims

To investigate the expression of claudins and Ki-67 in early GC cells and surrounding normal gastric mucosa.

Methods

A total of 53 early GC lesions removed via endoscopic mucosal resection or endoscopic submucosal resection were evaluated. All of the GCs were characterized as well to moderately differentiated adenocarcinoma. The labeling index (LI) of Ki-67 was calculated for each sample. To assess the prevalence of epithelial TJs, immunofluorescent staining for claudin-3, claudin-4, and claudin-7 was performed. The immunoreactivity was graded according to the percentage of stained cells.

Results

Claudin-3, claudin-4, and claudin-7 expression at TJs in GC and intestinal metaplasia were significantly higher than that in gastric mucosa with no intestinal metaplasia. The Ki-67 LI of GC specimens was inversely correlated with claudin-3 expression, but not with claudin-4 or claudin-7 expression. Claudin-3 expression was significantly lower at the submucosal invasive front of GCs.

Conclusions

The down-regulation of claudin-3 was associated with the proliferative potential of GC cells, indicating that claudins may have a pivotal role in the progression of GC.

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Acknowledgments

We thank Ms. Noriko Kamiya for the technical assistance. This work was supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan through a Grant-in-Aid for Scientific Research (C) 2010–2012 (no. 22590691).

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Authors and Affiliations

  1. Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Takuya Okugawa, Tadayuki Oshima, Xin Chen, Toshihiko Tomita, Hirokazu Fukui, Jiro Watari & Hiroto Miwa

  2. Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Kazutoshi Hori & Takayuki Matsumoto

Authors
  1. Takuya Okugawa
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  2. Tadayuki Oshima
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  3. Xin Chen
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  4. Kazutoshi Hori
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  5. Toshihiko Tomita
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  6. Hirokazu Fukui
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  7. Jiro Watari
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  8. Takayuki Matsumoto
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  9. Hiroto Miwa
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Correspondence to Tadayuki Oshima.

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Okugawa, T., Oshima, T., Chen, X. et al. Down-Regulation of Claudin-3 Is Associated with Proliferative Potential in Early Gastric Cancers. Dig Dis Sci 57, 1562–1567 (2012). https://doi.org/10.1007/s10620-012-2043-5

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  • DOI: https://doi.org/10.1007/s10620-012-2043-5

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