Changes in expression of hepatocyte growth factor (HGF) and its receptor, MET, are associated with formation and malignant progression of human tumors.
In preclinical GEC models, abrogation of HGF/MET signaling has been shown to induce tumor regression as well as inhibition of metastatic dissemination.
We have investigated the correlations among hepatocyte growth factor (HGF) mRNA expression, basic fibroblast growth factor (bFGF) mRNA expression, tumor microvessel density (MVD), and clinical pathological features of gastric cancer in Chinese patients.
Hepatocyte growth factor (HGF)-stimulated Met signaling influences tumor survival, growth and progression, all processes involving the transcription factor NF-kappaB.
It is tempting to associate the radiation-enhanced HGF secretion with an increased angiogenic potential of the tumor, which may be a factor in radioresistance.
Increased copy number gain and amplification of c-Met, the cell surface receptor for hepatocyte growth factor, has been shown to enhance tumor growth and invasiveness and promote metastasis in certain tumor types.
HGF is produced by several tissues, including neoplasms; it can therefore provide a stimulus for increased motility of malignant cells by both a paracrine and autocrine mechanism.
Surprisingly, we also found that short pretreatment of cells and tumors with exogenous HGF moderately but statistically significantly enhanced the antitumor effects of c-MET inhibition.
Due to the fact that the proto-oncogene c-Met encodes the high-affinity receptor for HGF, and the HGF-c-Met signaling plays a critical role in the tumor genesis, we further identified the partial correlation between SMYD3 and c-Met.
Growth factor receptor expression and activation, particularly for epidermal growth factor (EGF) and hepatocyte growth factor (HGF), in many endocrine and nonendocrine tumors is important in determining tumor recurrence, growth, and aggressiveness.
Because the hepatocyte growth factor (HGF)/MET pathway plays an important role in tumor-stroma interactions we next investigated the involvement of this pathway in tumor-stroma interactions leading to the decreased efficacy of adenoviral therapy.
Under hypoxic conditions, silencing of HIF-1β expression suppressed tumor cell growth and regulated the expression of tumor growth-related factors, such as vascular endothelial growth factor, epidermal growth factor, and hepatocyte growth factor.
With the goal to investigate the molecular basis of MET amplification (MET<sup>amp</sup>) and hepatocyte growth factor (HGF) autocrine-driven tumors in response to MET tyrosine kinase inhibitors (TKI) and neutralizing antibodies, we compared cancer cells harboring MET<sup>amp</sup> (MKN45 and MHCCH97H) or HGF-autocrine (JHH5 and U87) for their sensitivity and downstream biological responses to a MET-TKI (INC280) and an anti-MET monoclonal antibody (MetMab) in vitro, and for tumor inhibition in vivo.
Consistent with this observation, small-molecule inhibitors of c-Met were developed that antagonized c-Met/HGF-dependent phenotypes and tumor growth in mouse models.
In light of the inter-relationship between HGF/Met and other ligand receptor, combinatorial targeting strategies may provide opportunities for therapeutic advancement in this challenging tumour.
Our observation that combination therapy either failed to improve or even reduced survival in mice bearing Shh + HGF-induced medulloblastomas compared with monotherapy underscores the importance of preclinical testing of molecular-targeted therapies in animal models of tumors in which the targeted pathways are known to be active.
Immunostaining and real-time RT-PCR analysis of tumour specimens demonstrated coordinated expression of TrkB and HGF/c-Met in experimental and primary neuroblastomas.