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HGF/c-Met 在结直肠癌肝转移治疗中的作用。

Role of HGF/c-Met in the treatment of colorectal cancer with liver metastasis.

机构信息

Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.

Department of General Surgery, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

出版信息

J Biochem Mol Toxicol. 2019 Jun;33(6):e22316. doi: 10.1002/jbt.22316. Epub 2019 Mar 21.

Abstract

The system of hepatocyte growth factor (HGF) and its receptor c-Met plays a critical role in tumor invasive growth and metastasis. The mortality rate of colorectal cancer (CRC), one of the most commonly diagnosed malignancies, is increased by it gradual development into metastasis, most frequently in the liver. Overexpression of c-Met, the protein tyrosine kinase receptor for the HCF/scatter factor, has been implicated in the progression and metastasis of human colorectal carcinoma. In this study, we aimed to investigate the role of c-Met in CRC liver metastasis and illustrate the clinical impact of regulating HGF/c-Met signaling in patients with CRC liver metastasis. We found that (I) higher levels of c-Met expression (mRNA and Protein) in CRC liver metastasis than primary CRC by assessing the patient tissue samples; (II) a positive correlation of c-Met expression with tumor stages of CRC liver metastasis, as well as c-Met expression in CRC, live metastasis concurred with regional lymph node metastasis; (III) the clinical impact of downregulation of HGF/c-Met signaling on the reduction of proliferation and invasion in CRC liver metastasis. Therefore, we demonstrate that the regulation of HGF/c-Met pathways may be a promising strategy in the treatment of patients with CRC liver metastasis.

摘要

肝细胞生长因子(HGF)及其受体 c-Met 系统在肿瘤侵袭性生长和转移中起着关键作用。结直肠癌(CRC)是最常见的恶性肿瘤之一,其死亡率因逐渐发展为转移而增加,最常见于肝脏。HGF/scatter factor 的蛋白酪氨酸激酶受体 c-Met 的过表达与人类结直肠癌的进展和转移有关。在这项研究中,我们旨在研究 c-Met 在 CRC 肝转移中的作用,并阐明调节 HGF/c-Met 信号在 CRC 肝转移患者中的临床影响。我们发现:(I)通过评估患者组织样本,CRC 肝转移中 c-Met 的表达(mRNA 和蛋白)高于原发性 CRC;(II)c-Met 的表达与 CRC 肝转移的肿瘤分期呈正相关,以及 CRC 肝转移中的 c-Met 表达与区域淋巴结转移一致;(III)下调 HGF/c-Met 信号对 CRC 肝转移中增殖和侵袭的减少的临床影响。因此,我们证明了调节 HGF/c-Met 途径可能是治疗 CRC 肝转移患者的一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8717/6617765/7f6ce33ad022/JBT-33-na-g001.jpg

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