Department of Oncology, University of Torino, 10060 Candiolo, Italy.
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Int J Mol Sci. 2018 Dec 7;19(12):3920. doi: 10.3390/ijms19123920.
The 'onco-receptor' MET (Hepatocyte Growth Factor Receptor) is involved in the activation of the invasive growth program that is essential during embryonic development and critical for wound healing and organ regeneration during adult life. When aberrantly activated, MET and its stroma-secreted ligand HGF (Hepatocyte Growth Factor) concur to tumor onset, progression, and metastasis in solid tumors, thus representing a relevant target for cancer precision medicine. In the vast majority of tumors, wild-type behaves as a 'stress-response' gene, and relies on ligand stimulation to sustain cancer cell 'scattering', invasion, and protection form apoptosis. Moreover, the MET/HGF axis is involved in the crosstalk between cancer cells and the surrounding microenvironment. Pancreatic cancer (namely, pancreatic ductal adenocarcinoma, PDAC) is an aggressive malignancy characterized by an abundant stromal compartment that is associated with early metastases and resistance to conventional and targeted therapies. Here, we discuss the role of the MET/HGF axis in tumor progression and dissemination considering as a model pancreatic cancer, and provide a proof of concept for the application of dual MET/HGF inhibition as an adjuvant therapy in pancreatic cancer patients.
“肿瘤受体”MET（肝细胞生长因子受体）参与激活浸润性生长程序，该程序在胚胎发育过程中至关重要，对于成年期的伤口愈合和器官再生也至关重要。当异常激活时，MET 及其基质分泌的配体 HGF（肝细胞生长因子）共同导致实体瘤的肿瘤发生、进展和转移，因此成为癌症精准医学的一个相关靶点。在绝大多数肿瘤中，野生型 MET 表现为“应激反应”基因，依赖配体刺激来维持癌细胞“扩散”、浸润和免受凋亡的保护。此外，MET/HGF 轴参与癌细胞与周围微环境之间的串扰。胰腺癌（即胰腺导管腺癌，PDAC）是一种侵袭性恶性肿瘤，其特征是基质丰富，与早期转移和对常规及靶向治疗的耐药性有关。在这里，我们讨论了 MET/HGF 轴在肿瘤进展和播散中的作用，将其作为胰腺癌的模型，并提供了双重 MET/HGF 抑制作为辅助治疗在胰腺癌患者中的应用的概念验证。
