德国研究人员1日说，他们鉴定出115种与结肠癌转移相关的基因，这项成果将有望帮助早期诊断结肠癌患者的肿瘤是否有扩散危险。
癌细胞转移是导致结肠癌患者死亡的重要原因。为调查哪些基因促进癌细胞转移，德国马克斯·德尔布吕克分子医学中心和柏林沙里泰大学医院的研究人员分析了150份癌细胞转移和未转移的结肠癌患者的组织样本，结果鉴定出115个在原发病灶和转移癌细胞中都有的基因，由此找出了区别转移性肿瘤和非转移性肿瘤的基因标志。
研究人员进而又研究了其中一种名为“BAMBI”的基因。结果发现，这种基因在转移性肿瘤和转移癌细胞中比在非转移性肿瘤中更活跃。研究还显示，这种基因与Wnt－β和TGF－β两种重要的传导通路有关，从而促使癌细胞转移。
研究人员说，他们将继续研究另外114种基因，以更好地了解癌细胞转移的具体原因。（生物谷Bioon.com）
生物谷推荐原始出处：
Gastroenterology July 2009,doi:10.1053/j.gastro.2009.03.041
A Colorectal Cancer Expression Profile That Includes Transforming Growth Factor β Inhibitor BAMBI Predicts Metastatic Potential
Johannes Fritzmann, ?, Markus Morkel, Daniel Besser, Jan Budczies§, Frauke Kosel, Felix H. Brembeck, Ulrike Stein, ?, Iduna Fichtner, Peter M. Schlag, ? and Walter Birchmeier, ,
Department for Surgery and Surgical Oncology, Berlin, Germany
Max Delbrueck Center for Molecular Medicine, Berlin, Germany
Institute for Pathology, Charité-University Medical School, Berlin, Germany
Background & Aims
Much is known about the genes and mutations that cause colorectal cancer (CRC), yet only a few have been associated with CRC metastasis. We performed expression-profiling experiments to identify genetic markers of risk and to elucidate the molecular mechanisms of CRC metastasis.
Methods
We compared gene expression patterns between metastatic and nonmetastatic stage-matched human colorectal carcinomas by microarray analysis. Correlations between BAMBI and metastasis-free survival were examined by quantitative real-time polymerase chain reaction (PCR) using an independent set of human colon carcinomas. Human colon cancer cell lines were analyzed for BAMBI regulation, cell motility, and experimental metastasis.
Results
We established a signature of 115 genes that differentiated metastatic from nonmetastatic primary tumors. Among these, the transforming growth factor (TGF) β inhibitor BAMBI was highly expressed in approximately half of metastatic primary tumors and metastases but not in nonmetastatic tumors. BAMBI is a target of canonical Wnt signaling that involves the β-catenin coactivator BCL9-2. We observed an inverse correlation between level of BAMBI expression and metastasis-free survival time of patients. BAMBI inhibits TGF-β signaling and increases migration in colon cancer cells. In mice, overexpression of BAMBI caused colon cancer cells to form tumors that metastasized more frequently to liver and lymph nodes than control cancer cells.
Conclusions
BAMBI regulates CRC metastasis by connecting the Wnt/β-catenin and TGF-β-signaling pathways. The metastatic expression signature we describe, along with BAMBI levels, can be used in prognosis. Developmental signaling pathways appear to act in hierarchies and cooperate in tumor cell migration, invasion, and metastasis.
