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The Clinical Significance of Vimentin-Expressing Gastric Cancer Cells in Bone Marrow

  • Translational Research and Biomarkers
  • Published:
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Abstract

Background

Expression of the mesenchymal marker gene vimentin (VIM) in gastric cancer is associated with a more aggressive form of the disease and poor prognosis. Because epithelial mesenchymal transition (EMT) plays a critical role in the progression of gastric cancer, VIM expression was examined in the bone marrow (BM) of gastric cancer patients.

Methods

BM samples from 437 gastric cancer patients were collected and analyzed by quantitative RT-PCR. Expression of VIM protein in the primary lesions of resected gastric cancers was evaluated using immunohistochemistry. Furthermore, induction of VIM expression by TGF-β1 and hypoxia was evaluated in gastric cancer cells.

Results

VIM mRNA expression increased concordantly with clinical staging and was significantly associated with tumor invasion and lymph node metastasis (P < .0001). Though cancer cells in the primary lesions did not stain with VIM antibody, some of the cells invading the intratumoral vessels were strongly positive for VIM, but were negative for E-cadherin. Hypoxic conditions and treatment with TGF-β1 induced VIM expression and repressed E-cadherin in gastric cancer cells, coupled with an alteration of cellular morphology.

Conclusions

We found that gastric cancer cells undergo EMT in BM to survive and metastasize. These findings suggest that isolated tumor cells have the potential to undergo EMT, which could increase the malignancy of gastric cancer.

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Acknowledgment

We thank T. Shimooka, K. Ogata, M. Kasagi, Y. Nakagawa, and T. Kawano for their technical assistance. This work was supported in part by the following grants and foundations: CREST, Japan Science and Technology Agency (JST); Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, grant numbers 20390360, 20591547, 20790960, 21591644, 21791295, 21791297, 215921014, and 21679006; NEDO (New Energy and Industrial Technology Development Organization) Technological Development for Chromosome Analysis.

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Authors and Affiliations

  1. Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan

    Masaaki Iwatsuki MD, Koshi Mimori MD, Hideshi Ishii MD, Takehiko Yokobori MD & Masaki Mori MD, FACS

  2. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Masaaki Iwatsuki MD & Hideo Baba MD

  3. Gastric Surgery Division, National Cancer Center Hospital, Tokyo, Japan

    Takeo Fukagawa MD & Mitsuru Sasako MD

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  1. Masaaki Iwatsuki MD
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Correspondence to Masaki Mori MD, FACS.

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Iwatsuki, M., Mimori, K., Fukagawa, T. et al. The Clinical Significance of Vimentin-Expressing Gastric Cancer Cells in Bone Marrow. Ann Surg Oncol 17, 2526–2533 (2010). https://doi.org/10.1245/s10434-010-1041-0

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