Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Ann Surg Oncol. 2010 Sep;17(9):2526-33. doi: 10.1245/s10434-010-1041-0. Epub 2010 Apr 1.
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.
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.
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.
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.
胃癌中间质标志物基因波形蛋白（VIM）的表达与疾病侵袭性更强和预后不良相关。由于上皮间质转化（EMT）在胃癌进展中起着关键作用，因此研究人员检测了胃癌患者骨髓（BM）中的 VIM 表达。
收集了 437 名胃癌患者的 BM 样本，并通过定量 RT-PCR 进行分析。使用免疫组织化学评估 VIM 蛋白在切除的胃癌原发灶中的表达。此外，还评估了 TGF-β1 和缺氧诱导胃癌细胞 VIM 表达的情况。
VIM mRNA 表达与临床分期一致增加，与肿瘤侵袭和淋巴结转移显著相关（P <.0001）。尽管原发灶中的癌细胞不与 VIM 抗体染色，但一些浸润肿瘤内血管的细胞强烈表达 VIM，但不表达 E-钙黏蛋白。缺氧条件和 TGF-β1 处理诱导胃癌细胞中 VIM 表达和 E-钙黏蛋白表达下调，同时伴有细胞形态的改变。
研究人员发现胃癌细胞在 BM 中经历 EMT 以存活和转移。这些发现表明，分离的肿瘤细胞有可能经历 EMT，这可能会增加胃癌的恶性程度。
