Babyatsky Mark, Lin Jing, Yio Xianyang, Chen Anli, Zhang Jie-yu, Zheng Yan, Twyman Christina, Bao Xiuliang, Schwartz Myron, Thung Swan, Lawrence Werther J, Itzkowitz Steven
The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, The Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1069, New York, NY 10029-6574, USA.
Clin Exp Metastasis. 2009;26(2):143-51. doi: 10.1007/s10585-008-9224-9. Epub 2008 Nov 2.
Deaths from colorectal cancer are often due to liver metastasis. Trefoil factor-3 (TFF3) is expressed by normal intestinal epithelial cells and its expression is maintained throughout the colon adenoma-carcinoma sequence. Our previous work demonstrated a correlation between TFF3 expression and metastatic potential in an animal model of colon cancer. The aim of this study was to determine whether TFF3 is expressed in human colon cancer liver metastasis (CCLM) and whether inhibiting TFF3 expression in colon cancer cells would alter their invasive potential in vitro. Human CCLMs were analyzed at the mRNA and protein level for TFF3 expression. Two highly metastatic rat colon cancer cell lines that either natively express TFF3 (LN cells) or were transfected with TFF3 (LPCRI-2 cells), were treated with two rat TFF3 siRNA constructs (si78 and si365), and analyzed in an in vitro invasion assay. At the mRNA and protein level, TFF3 was expressed in 17/17 (100%) CCLMs and 10/11 (91%) primary colon cancers, but not in normal liver tissue. By real time PCR, TFF3 expression was markedly inhibited by both siRNA constructs in LN and LPCRI-2 cells. The si365 and si78 constructs inhibited invasion by 44% and 53%, respectively, in LN cells, and by 74% and 50%, respectively, in LPCRI-2 cells. These results provide further evidence that TFF3 contributes to the malignant behavior of colon cancer cells. These observations may have relevance for designing new diagnostic and treatment approaches to colorectal cancer.
结直肠癌死亡通常归因于肝转移。三叶因子3（TFF3）由正常肠上皮细胞表达，且其表达在整个结肠腺瘤-癌序列中得以维持。我们之前的研究表明在结肠癌动物模型中TFF3表达与转移潜能之间存在关联。本研究的目的是确定TFF3是否在人结肠癌肝转移（CCLM）中表达，以及抑制结肠癌细胞中TFF3表达是否会改变其体外侵袭潜能。对人CCLM在mRNA和蛋白质水平分析TFF3表达。两种高转移性大鼠结肠癌细胞系，一种天然表达TFF3（LN细胞），另一种用TFF3转染（LPCRI-2细胞），用两种大鼠TFF3 siRNA构建体（si78和si365）处理，并在体外侵袭试验中进行分析。在mRNA和蛋白质水平，TFF3在17/17（100%）的CCLM和10/11（91%）的原发性结肠癌中表达，但在正常肝组织中不表达。通过实时PCR，两种siRNA构建体在LN和LPCRI-2细胞中均显著抑制TFF3表达。si365和si78构建体在LN细胞中分别将侵袭抑制了44%和53%，在LPCRI-2细胞中分别将侵袭抑制了74%和50%。这些结果提供了进一步证据表明TFF3促成结肠癌细胞的恶性行为。这些观察结果可能与设计结直肠癌新的诊断和治疗方法相关。
