The clinical significance of vimentin-expressing gastric cancer cells in bone marrow.
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-beta1 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-beta1 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.
Iwatsuki
Masaaki
M
Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Mimori
Koshi
K
Fukagawa
Takeo
T
Ishii
Hideshi
H
Yokobori
Takehiko
T
Sasako
Mitsuru
M
Baba
Hideo
H
Mori
Masaki
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010100:Oxygen / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism
D015820:Cadherins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D010100:Oxygen