Overall, c-met protein staining was noted in 36 of 43 (84%) primary prostate cancer samples versus 2 of 11 (18%) benign prostate hyperplasia samples (p < 0.0001) and in 4 of 4 (100%) lymph node metastases, 23 of 23 (100%) bone marrow metastases and 1 of 3 (33%) other metastatic sites.
Background C-Met, which is frequently activated in multiple cancers, has been implicated in tumor formation, progression, metastasis, angiogenesis, and resistance to multiple therapies.
The MET receptor tyrosine kinase, the receptor for hepatocyte growth factor (HGF), has been implicated in cancer growth, invasion, migration, angiogenesis, and metastasis in a broad variety of human cancers, including human hepatocellular carcinoma (HCC).
Patients with MET alterations demonstrated a significantly shorter median time to metastasis/recurrence (1.0 vs 10.4 months, P = 0.044, multivariable) and a poorer survival (30.6 vs 58.4 months, P = 0.013, univariate only).
The expression of p53, beta-hCG, c-Met, and uMAGE in primary tumors was significantly higher in the presence of nodal micrometastases vs no metastases (P =.03).
For this purpose, tumor samples were analyzed for c-MET expression by immunohistochemistry (IHC), for c-MET copy number alterations by fluorescence in situ hybridization (FISH), and for c-MET mutations by next generation sequencing (NGS) in a retrospective cohort of 90 primary ccRCC of patients with metastases treated by first-line sunitinib.
High expression of the MET receptor has been shown to correlate with increased tumor growth and metastasis, poor prognosis and resistance to radiotherapy.
MET mutational analyses were performed in tumors, adjacent normal tissues as well as in lymph nodes with no metastasis nonadherent to tumor tissues using Sanger sequencing after PCR.
These results suggest that the amplification and overexpression of c-met gene do not play a different role in the progression and metastasis of EBV-positive and EBV-negative gastric carcinomas.
Elevated activation of the receptor tyrosine kinase (RTK) MET is frequent in RMS and is thought to cause increased tumor metastasis and lack of differentiation.
Inhibition of the HGF-Met receptor pathway and tumor angiogenesis by NK4 gene expression has potential therapeutic value toward inhibition of invasion, growth, and metastasis of colon cancer.
Inhibition of MET expression or function leads to (i) a decreased expression of the early myogenic marker MyoD, (ii) a decreased ability of ARMS cells to metastasize to bone marrow cavities, (iii) downregulation of CXCR4 receptor expression and (iv) a decreased migration of MET-depleted cells towards gradients of HGF and SDF-1.
Our data unequivocally demonstrates the autocrine dependency of HGF/SF-Met-induced transformation and metastasis in this system and supports the theory that the inappropriate expression of HGF/SF and Met proteins could play a role in the development and spread of human tumors.
The epithelial-to-mesenchymal transition (EMT) and the reverse process (the mesenchymal-to-epithelial transition [MET]) have been shown to be associated with tumor cell invasion and metastasis in different carcinomas.
MET GCN gain was observed in 14.7 % (25/170), which correlated with advanced stage (P = 0.037), presence of distant metastasis (P = 0.006), and short overall survival (OS) (P = 0.009).