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Carbonic anhydrase-related protein VIII increases invasiveness of non-small cell lung adenocarcinoma

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Abstract

Carbonic anhydrase-related protein VIII (CA-RP VIII) is believed to be an oncofetal antigen and is overexpressed in colorectal and non-small cell lung cancer. However, the pathobiological properties of CA-RP VIII in lung cancer remain unclear. In the present study, we examined ultrastructural changes caused by exogenous CA-RP VIII expression in a well-differentiated lung adenocarcinoma cell line, PC-9. Many vacuoles lined by cilia, sometimes large vacuoles pushing the nuclei to one side, were found in the cytoplasm of CA-RP VIII-expressing PC-9 cells, but not in control PC-9 cells. Moreover, signet-ring cells containing abundant intracytoplasmic mucin were often found among CA-RP VIII-expressing PC-9 cells, but rarely among control PC-9 cells. We subsequently examined CA-RP VIII expression in atypical adenomatous hyperplasia and early-stage lung adenocarcinoma (Stage Ia). Significant expression of CA-RP VIII was observed in invasive lung adenocarcinoma but not in noninvasive adenocarcinoma. Interestingly, CA-RP VIII was strongly expressed in signet-ring cell cancer and invasive mucinous adenocarcinoma components. CA-RP VIII also appeared to enhance the invasiveness of PC-9 cells in Matrigel invasion assay. The present findings suggest that CA-RP VIII expression in lung adenocarcinoma is related to cancer cell invasion.

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Acknowledgements

We thank Mr. Yamaguchi, Takuya, Ms. Nakamura, Naoyo (Department of Pathology, Kochi Medical School), and Ms. Matumura, Rumi (Division of Molecular Biology, Kochi Medical School) for skillful technique. This study was supported by grants from the Japanese Ministry of Education, Science, and Culture (KAKEN 17590270, 17590654, 15590656) and the Medical Research Fund of Kochi Medical School.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan

    Tsuyoshi Ishihara, Isao Nishimori, Tomoko Minakuchi & Saburo Onishi

  2. Department of Pathology, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan

    Tamotsu Takeuchi, Yoshihiro Adachi & Yuji Ohtsuki

  3. First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Senbaru, Nishihara, Okinawa, 903-0213, Japan

    Jiro Fujita

  4. Department of Laboratory Medicine and Pathology, National Hospital Organization Fukuyama Medical Center, Okinogami 4-14-17, Fukuyama, Hiroshima, 720-8520, Japan

    Hiroshi Sonobe

Authors
  1. Tsuyoshi Ishihara
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  2. Tamotsu Takeuchi
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  3. Isao Nishimori
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  4. Yoshihiro Adachi
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  5. Tomoko Minakuchi
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  6. Jiro Fujita
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  7. Hiroshi Sonobe
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  8. Yuji Ohtsuki
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  9. Saburo Onishi
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Correspondence to Tamotsu Takeuchi.

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Ishihara, T., Takeuchi, T., Nishimori, I. et al. Carbonic anhydrase-related protein VIII increases invasiveness of non-small cell lung adenocarcinoma. Virchows Arch 448, 830–837 (2006). https://doi.org/10.1007/s00428-006-0199-0

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  • DOI: https://doi.org/10.1007/s00428-006-0199-0

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