Annals of Surgical Oncology

, Volume 17, Issue 9, pp 2526–2533

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

  • Masaaki Iwatsuki
  • Koshi Mimori
  • Takeo Fukagawa
  • Hideshi Ishii
  • Takehiko Yokobori
  • Mitsuru Sasako
  • Hideo Baba
  • Masaki Mori
Translational Research and Biomarkers

DOI: 10.1245/s10434-010-1041-0

Cite this article as:
Iwatsuki, M., Mimori, K., Fukagawa, T. et al. Ann Surg Oncol (2010) 17: 2526. doi:10.1245/s10434-010-1041-0

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.

Supplementary material

10434_2010_1041_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 15 kb)

Copyright information

© Society of Surgical Oncology 2010

Authors and Affiliations

  • Masaaki Iwatsuki
    • 1
    • 2
  • Koshi Mimori
    • 1
  • Takeo Fukagawa
    • 3
  • Hideshi Ishii
    • 1
  • Takehiko Yokobori
    • 1
  • Mitsuru Sasako
    • 3
  • Hideo Baba
    • 2
  • Masaki Mori
    • 1
  1. 1.Department of Surgical Oncology, Medical Institute of BioregulationKyushu UniversityBeppuJapan
  2. 2.Department of Gastroenterological Surgery, Graduate School of Medical SciencesKumamoto UniversityKumamotoJapan
  3. 3.Gastric Surgery DivisionNational Cancer Center HospitalTokyoJapan