c-Met Expression Research Articles

11P - hTERT mediated c-MET expression is p53 dependent in cancer cells

11P - hTERT mediated c-MET expression is p53 dependent in cancer cells

Carcinoma associated fibroblasts derived from oral squamous cell carcinoma promote lymphangiogenesis via c-Met/PI3K/AKT in vitro.

Carcinoma-associated fibroblasts (CAFs) are dominant components of the tumor microenvironment (TME) that promote the development, progression and metastasis of cancer. c-Met is a receptor of the hepatocyte growth factor (HGF), which is involved in lymphangiogenesis. Currently, the roles of CAFs during lymphangiogenesis are unknown. It has been hypothesized that CAFs contribute to lymphangiogenesis of oral squamous cell carcinoma (OSCC) via a HGF/c-Met complex. The expression of HGF in OSCC was determined using CAFs derived from OSCC tissue and it was demonstrated that HGF is overexpressed in OSCC-derived CAFs. It was also revealed that c-Met was highly expressed in human lymphatic endothelial cells (HLECs) when co-cultured with CAFs. Furthermore, it was demonstrated that recombinant human HGF significantly enhanced the proliferation, migration, invasion and tube formation of HLECs. By contrast, the inhibition of c-Met expression suppressed the aforementioned biological activities and also downregulated the expression of c-Met, phosphoinositide 3-kinase and phosphorylated protein kinase B. Taken together, these data demonstrate that c-Met is associated with the regulation of lymphangiogenesis. Thus, the results of the present study indicate that c-Met may be a promising novel therapeutic target to treat patients with OSCC.

MicroRNA-206 prevents the pathogenesis of hepatocellular carcinoma by modulating expression of met proto-oncogene and cyclin-dependent kinase 6 in mice.

In summary, this study defines a potentially critical role of microRNA-206 in preventing the growth of HCC and suggests its use as a potential therapeutic strategy for this malignancy. (Hepatology 2017;66:1952-1967).

Prognostic Value of c-MET Expression in Patients With Pancreatic Cancer Receiving Adjuvant and Neoadjuvant Chemoradiation Therapy

To determine the prognostic significance of c-MET expression and develop a predictor of distant failure in patients with resectable pancreatic cancer treated with chemoradiation. We used a tissue microarray to study protein expression by immunohistochemistry in 102 patients treated surgically for pancreatic cancer. Two cores per patient were blindly scored from 0 (no staining) to 3 (strong staining) by a single pathologist. The Kaplan-Meier method was used to determine time to local and distant failure, overall survival, and progression-free survival. P values were calculated with the log-rank test. High tumor expression of c-MET was associated with a shorter time to distant failure in patients receiving neoadjuvant (n=23) or neoadjuvant therapy (n=73) (median 8.9months vs 22.0months, P=.0010). We then examined the ability of incorporating 2 known biomarkers, thymidylate synthase and DPC4 (SMAD4), with c-MET to risk-stratify patients. This multi-protein predictor divided our cohort into groups of similar numbers and was predictive of distant failure (median 13.4months vs 24.2months, P=.0094) but not of local control. c-MET is potentially predictive of distant failure. Using c-MET, DPC4, and thymidylate synthase, we developed a multi-protein predictor that could be used to risk-stratify patients and guide decisions regarding the sequencing of locoregional and systemic therapies in pancreatic cancer.

PS06.04 Clinicopathologic Correlation of MACC1 and c-Met Expression in Lung Adenocarcinoma: Topic: Pathology

PS06.04 Clinicopathologic Correlation of MACC1 and c-Met Expression in Lung Adenocarcinoma: Topic: Pathology

Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression.

In preclinical models, c-Met promotes survival of renal cancer cells through the regulation of programmed death-ligand 1 (PD-L1). However, this relationship in human clear cell renal cell carcinoma (ccRCC) is not well characterized. We evaluated c-Met expression in ccRCC patients using paired primary and metastatic samples and assessed the association with PD-L1 expression and other clinical features. Areas with predominant and highest Fuhrman nuclear grade (FNG) were selected. c-Met expression was evaluated by IHC using an anti-Met monoclonal antibody (MET4 Ab) and calculated by a combined score (CS, 0–300): intensity of c-Met staining (0–3) x % of positive cells (0–100). PD-L1 expression in tumor cells was previously assessed by IHC and PD-L1+ was defined as PD-L1 > 0% positive cells. Our cohort consisted of 45 pairs of primary and metastatic ccRCC samples. Overall, c-Met expression was higher in metastatic sites compared to primary sites (average c-Met CS: 55 vs. 28, p = 0.0003). Higher c-Met expression was associated with higher FNG (4 vs. 3) in primary tumors (average c-Met CS: 52 vs. 20, p = 0.04). c-Met expression was numerically greater in PD-L1+ vs. PD-L1- tumors. Higher c-Met expression in metastatic sites compared to primary tumors suggests that testing for biomarkers of response to c-Met inhibitors should be conducted in metastases. While higher c-Met expression in PD-L1+ tumors requires further investigation, it supports exploring these targets in combination clinical trials.

Huaier extract enhances the treatment efficacy of paclitaxel in breast cancer cells via the NF-κB/IκBα pathway.

Breast cancer is considered as the most common malignant disease in women. Huaier extract, a type of traditional Chinese medicine, has been found to have antitumor activity. In the present study, we aimed to investigate whether the combined treatments of paclitaxel and Huaier extract may improve treatment efficacy in breast cancer cells. Human breast cancer cell lines MCF-7 and MDA-MB-231 were used to evaluate the antitumor efficacy of Huaier extract and paclitaxel both invitro and invivo. Using proliferation assays and flow cytometry, we found that both Huaier extract and paclitaxel decreased cell viability and induced cell apoptosis in a time-and dose-dependent manner. The combined treatments were more effective than monotherapy. Huaier extract induced cycle arrest in the G0/G1phase, and paclitaxel arrested the cell cycle in the G2/Mphase. Furthermore, the results of real-time PCR and western blotting revealed that Huaier extract decreased p65 and c-Met expression and increased IκBα expression, while paclitaxel increased p65 expression and reduced IκBα and c-Met expression. Consistent with the invitro results, both Huaier extract and paclitaxel exerted a significant inhibitory effect on xenografted tumor growth, and the combined therapies revealed the most marked inhibitory effect. Collectively, our results indicated that Huaier extract increased the antitumor effect of paclitaxel therapy in breast cancer cells. The molecular mechanisms may be involved in the inhibition of the NF-κB pathway and c-Met expression.

HGF potentiates extracellular matrix-driven migration of human myoblasts: involvement of matrix metalloproteinases and MAPK/ERK pathway

BackgroundThe hepatocyte growth factor (HGF) is required for the activation of muscle progenitor cells called satellite cells (SC), plays a role in the migration of proliferating SC (myoblasts), and is present as a soluble factor during muscle regeneration, along with extracellular matrix (ECM) molecules. In this study, we aimed at determining whether HGF is able to interact with ECM proteins, particularly laminin 111 and fibronectin, and to modulate human myoblast migration.MethodsWe evaluated the expression of the HGF-receptor c-Met, laminin, and fibronectin receptors by immunoblotting, flow cytometry, or immunofluorescence and used Transwell assays to analyze myoblast migration on laminin 111 and fibronectin in the absence or presence of HGF. Zymography was used to check whether HGF could modulate the production of matrix metalloproteinases by human myoblasts, and the activation of MAPK/ERK pathways was evaluated by immunoblotting.ResultsWe demonstrated that human myoblasts express c-Met, together with laminin and fibronectin receptors. We observed that human laminin 111 and fibronectin have a chemotactic effect on myoblast migration, and this was synergistically increased when low doses of HGF were added. We detected an increase in MMP-2 activity in myoblasts treated with HGF. Conversely, MMP-2 inhibition decreased the HGF-associated stimulation of cell migration triggered by laminin or fibronectin. HGF treatment also induced in human myoblasts activation of MAPK/ERK pathways, whose specific inhibition decreased the HGF-associated stimulus of cell migration triggered by laminin 111 or fibronectin.ConclusionsWe demonstrate that HGF induces ERK phosphorylation and MMP production, thus stimulating human myoblast migration on ECM molecules. Conceptually, these data state that the mechanisms involved in the migration of human myoblasts comprise both soluble and insoluble moieties. This should be taken into account to optimize the design of therapeutic cell transplantation strategies by improving the migration of donor cells within the host tissue, a main issue regarding this approach.

Clinicopathological impacts of high c-Met expression in head and neck squamous cell carcinoma: a meta-analysis and review.

High c-Met expression has been observed in head and neck squamous cell carcinoma (HNSCC). However, its clinicopathological impact remains controversial. We performed this meta-analysis to evaluate the pathologic and prognostic impacts of c-Met overexpression in patients with HNSCC. A systematic computerized search of the electronic databases was carried out. From 16 studies, 1,948 patients with HNSCC were included in the meta-analysis. Compared with HNSCCs showing low c-Met expression, tumors with high c-Met expression were significantly associated with higher rate of lymph node metastasis (odds ratio = 3.26, 95% CI: 2.27–4.69, P < 0.00001) and higher T stage (odds ratio = 1.33, 95% CI: 1.03–1.71, P = 0.03). In addition, patients with c-Met-high HNSCC showed significantly worse disease-free survival (hazard ratio = 1.49, 95% CI: 1.04–2.14, P = 0.03) and overall survival (hazard ratio = 1.83, 95% CI: 1.29–2.60, P = 0.0007) than those with c-Met-low tumor. In conclusion, this meta-analysis demonstrates that high c-Met expression is significantly associated with worse pathological features and prognosis, indicating c-Met overexpression is an adverse prognostic marker for patients with HNSCC.

MicroRNA-182 targets protein phosphatase 1 regulatory inhibitor subunit 1C in glioblastoma.

Glioblastoma (GBM) is an incurable cancer, with mean post-diagnosis survival time of 14-16 months. Metagenomic analysis by The Cancer Genome Atlas (TCGA) program has identified microRNA-182-5p (miR-182-5p or miR-182) as the only miRNA associated with favorable disease prognosis and temozolomide (TMZ) susceptibility. Previous reports have indicated that miR-182 down regulates expression of BCL2L12, c-MET, and HIF2A. However, other messenger RNA (mRNA) targets of miR-182 have not been validated which would explain its association with a favorable disease prognosis. In situ analysis revealed that protein phosphatase 1 regulatory inhibitor subunit 1C (PPP1R1C) is a putative target of miR-182. PPP1R1C protein and RNA expression as assessed by tissue microarray and quantitative real time PCR, respectively, was inversely correlated to miR-182 expression in glioblastoma patients and in the metastatic glioblastoma cell line U87-MG. Reporter assays using PPP1R1C 3′ untranslated region (UTR) showed that miR-182 can interact with the wild-type but not a miR-182-5-seed mutant. Ectopic expression of miR-182 mimic in the U87-MG cell line significantly decreased proliferation as well as suppressed in vitro migration and invasion. Opposite observations were made when the non-malignant neuronal cell line HCN-2 was transfected with anti-miR-182 antagomir. The miR-182 mimic or siRNA targeting PPP1R1C induced TMZ susceptibility indicating that decreased susceptibility to TMZ in GBM patients might be attributed to high expression of PPP1R1C. Inverse correlation of PPP1R1C mRNA and miR-182 levels in 20 GBM patients confirmed the same. Cumulatively, our results indicate that loss of miR-182 leads to increased expression of PPP1R1C which in part explain disease progression and resistance to TMZ therapy.

Overexpression of miR-101 promotes TRAIL-induced mitochondrial apoptosis in papillary thyroid carcinoma by targeting c-met and MCL-1.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) induces apoptosis in malignant cells, but not in normal cells. As papillary thyroid carcinoma cells broadly expressed TRAIL receptors (death receptor 4 and death receptor 5) on their surface, TRAIL is considered as a promising drug for treatment of papillary thyroid carcinoma. However, resistance to TRAIL still be a big obstacle to achieve a satisfactory effect for cancer therapy. Here, we found that overexpression of miR-101 was able to sensitize papillary thyroid carcinoma cells to TRAIL treatment in vitro and in vivo. Mechanically, we found that genes of c-met and MCL-1 were the targets of miR-101. Overexpression of miR-101 in TPC-1 significantly decreased the cellular protein levels of c-met and MCL-1, and thus inhibiting the PI3K/AKT pathway and reducing the resistance to TRAIL-induced mitochondrial apoptosis. Enforced expression of either c-met or MCL-1 could partially inhibit the miR-101 promoted apoptosis in TRAIL-treated TPC-1 cells. These results indicated that miR-101-c-met/MCL-1 axis determined the sensitivity of TRAIL to thyroid cancer in some extent. Combination with TRAIL and miR-101 may represent a novel approach to kill papillary thyroid carcinoma cells efficiently.

Expression of c-Met and hepatocyte growth factor in various gastric pathologies and its association with Helicobacter pylori infection.

Activation of the hepatocyte growth factor (HGF)/c-Met signaling pathway was identified to be associated with malignant tumors. The present study aimed at determining the expression of HGF and c-Met in gastric carcinogenesis and its association with Helicobacter pylori infection. Gastric biopsies were obtained from 160 H. pylori-negative and -positive patients, including those with chronic gastritis, intestinal metaplasia, dysplasia and gastric cancer (GC). Proteins were extracted from GES-1, gastric epithelial, and AGS, gastric adenocarcinoma, cells following co-culture with H. pylori in vitro. The expression of HGF and c-Met in gastric tissues or cells was determined using immunohistochemistry and western blot analysis. The expression of c-Met increased in GC tissues (72.5%) compared with that in pre-cancerous lesions (17.5, 17.5 and 30%). Additional analysis identified that the expression of HGF and c-Met was significantly increased in the presence of H. pylori infection in dysplasia and gastric cancer samples. Furthermore, H. pylori may activate the HGF/c-Met signaling pathway in vitro, which may contribute to gastric carcinogenesis.

Clinicopathological impacts of high c-Met expression in renal cell carcinoma: a meta-analysis and review.

c-Met overexpression has been observed in renal cell carcinoma (RCC). However, its clinicopathological impacts remain uncertain. We performed this meta-analysis to evaluate the pathologic and prognostic impacts of high c-Met expression in patients with RCC. A systematic computerized search of the electronic databases PubMed and Embase was performed. From 12 studies, 1,724 patients with RCC were included in the meta-analysis. Compared with RCCs showing low c-Met expression, tumors with high c-Met expression showed significantly higher nuclear grade (odds ratio = 2.45 [95% CI: 1.43–4.19], P = 0.001) and pT stage (odds ratio = 2.18 [95% CI: 1.27–3.72], P = 0.005). In addition, patients with c-Met-high RCC showed significantly worse overall survival than those with c-Met-low tumor (hazard ratio = 1.32 [95% CI: 1.12–1.56], P = 0.0009). In conclusion, this meta-analysis demonstrates that high c-Met expression correlate with significantly worse pathological features and overall survival, indicating c-Met overexpression is a potential adverse prognostic marker for patients with RCC.

Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer

ABSTRACTColorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. We analyzed 26 MSI-High and 558 non-MSI-High CRC tumors. BRCA2 mutations were highly enriched (50%) in MSI-High CRC. Immunohistochemistry showed that BRCA2-mutated MSI-High CRC had high c-MET (64%) expression compared with BRCA-WT (17%). We hypothesized a mechanistic link between BRCA2-deficiency and c-MET overexpression and synergistic interaction between drugs that treat BRCA-deficient tumors (mitomycin C (MMC) or PARP inhibitors) and c-MET inhibitors (crizotinib). We tested CRC cell lines for sensitivity to MMC plus crizotinib or other drug combinations including PARP-inhibitors. Combined treatment of tumor cells with crizotinib and MMC led to increased apoptosis as compared with each drug alone. Additionally, combination treatment with increasing concentrations of both drugs demonstrated a synergistic anti-cancer effect (CI = 0.006–0.74). However, we found no evidence for c-MET upregulation upon effective BRCA2 knockdown in tumor cells −/+DNA damage. Although we found no mechanistic link between BRCA2 deficiency and c-MET overexpression, c-MET is frequently overexpressed in CRC and BRCA2 is mutated especially in MSI-H CRC. The combination of crizotinib with MMC appeared synergistic regardless of MSI or BRCA2 status. Using an in-vivo CRC xenograft model we found reduced tumor growth with combined crizotinib and MMC therapy (p = 0.0088). Our preclinical results support clinical testing of the combination of MMC and crizotinib in advanced CRC. Targeting cell survival mediated by c-MET in combination with targeting DNA repair may be a reasonable strategy for therapy development in CRC or other cancers.

684P - Targeting c-met and DNA double-strand break (DSB) repair pathways for BRCA-mutated gastric carcinomas

Background: In the present study, we underline the importance of combining c-Met Inhibitor (Inh.) and DSB repair Inhibitor (PARP Inh.) with the goal of accomplishing a synergistic therapeutic strategy in BRCA-mutated gastric carcinomas. Methods: Firstly, to verify whether c-Met affects tumor response to PARP Inh., AGS (low c-Met expression) and Hs746T (high c-Met expression) cell lines, were subjected to knockdown c-Met expression, in the presence of PARP Inh. (NU1025). Subsequently, we examined the correlation between BRCA1/2 and c-Met. We knocked down BRCA1/2 expression in AGS and Hs746T cells and treated them with PARP Inh. Next, we examined the effects of combining c-Met Inh. (SU11274) and PARP Inh. (NU1025), measured by MTT, clonogenic cell survival and Annexin, assays. We also evaluated the effect of combining PARP Inh. and c-Met Inh. in AGS/Hs746T xenograft tumor models. AGS/Hs746T -pcDNA3 and AGS/Hs746T -siBRCA cells were injected into SCID mice. Tumor sizes were measured every 3 days. DNA damage was assessed by γ-H2AX staining. Results: Silence of Met expression promoted Hs746T cells more sensitive to PARP Inh. to similar levels as the AGS cells, as indicated by decreased cell viability. Silence of BRCA1/2 expression sensitized only AGS cells, signifying that increased expression of c-Met renders cells resistant to PARP Inh. in the context of inactivating BRCA1/2. Combining c-Met Inh. and PARP Inh. suppressed cell growth and clonogenicity and enhanced apoptosis in both AGS and Hs746T cells. The dual inhibition was demonstrated to be even more successful when cells were knockdown for BRCA1/2. Also, co-inhibition treatment substantially reduced tumor growth to AGS/Hs746T -pcDNA3 and more even effectively to AGS/Hs746T –siBRCA1/2 xenograft models, compared to either Inh. alone. DNA damage was higher in AGS/Hs746T –siBRCA1/2 compare to AGS/Hs746T -pcDNA3 xenograft models. Conclusions: BRCA deficiency renders gastric tumor cells sensitive to PARP inhibition. In addition, treatment with c-Met Inh. enhanced Hs746T sensitivity to the PARP Inh. Our data demonstrate that dual Met/PARP inhibition is synergistic providing an effective therapeutic strategy in BRCA-mutated gastric carcinomas. Legal entity responsible for the study: M.V. Karamouzis Funding: None Disclosure: All authors have declared no conflicts of interest.

Salvianolic acid A reverses cisplatin resistance in lung cancer A549 cells by targeting c-met and attenuating Akt/mTOR pathway

Drug resistance is one of the leading causes of chemotherapy failure in non-small cell lung cancer (NSCLC) treatment. The purpose of this study was to investigate the role of c-met in human lung cancer cisplatin resistance cell line (A549/DDP) and the reversal mechanism of salvianolic acid A (SAA), a phenolic active compound extracted from Salvia miltiorrhiza. In this study, we found that A549/DDP cells exert up-regulation of c-met by activating the Akt/mTOR signaling pathway. We also show that SAA could increase the chemotherapeutic efficacy of cisplatin, suggesting a synergistic effect of SAA and cisplatin. Moreover, we revealed that SAA enhanced sensitivity to cisplatin in A549/DDP cells mainly through suppression of the c-met/AKT/mTOR signaling pathway. Knockdown of c-met revealed similar effects as that of SAA in A549/DDP cells. In addition, SAA effectively prevented multidrug resistance associated protein1 (MDR1) up-regulation in A549/DDP cells. Taken together, our results indicated that SAA suppressed c-met expression and enhanced the sensitivity of lung adenocarcinoma A549 cells to cisplatin through AKT/mTOR signaling pathway.

Endoplasmic reticulum stress restrains hepatocyte growth factor expression in hepatic stellate cells and rat acute liver failure model

The aim of this study was to test whether endoplasmic reticulum (ER) stress suppresses hepatocyte growth factor (HGF) expression in hepatic stellate cells (HSCs) and whether ER stress plays a role in alleviating d-Galactosamine and Lipopolysaccharide (D-GalN/LPS)-induced acute liver failure (ALF) by regulating HGF expression. Rat HSCs line HSC-T6 were treated with the ER stress inducers tunicamycin or thapsigargin, and ER stress inhibitors sodium 4-phenylbutyrate (4-PBA) or salubrinal, respectively. Recombinant lentivirus containing eukaryotic translation initiation factor 2α (eIf2α), named LV-eIf2α-shRNA-GFP was produced to block eIf2α activated by ER stress. A rat ALF model was created by intraperitoneal injection of D-GalN/LPS, and 100 mg/kg 4-PBA was injected 6 h before injection as an inhibitor of ER stress. Levels of HGF, c-Met, vascular endothelial growth factor (VEGF), GRP78, eIf2α, phospho-eIF2α, ATF4 and CHOP in vitro and in vivo were measured. Our results demonstrated that ER stress stimulated VEGF but inhibited HGF expression in HSC-T6 cells. Both the stimulation of VEGF and the inhibition of HGF could be partly prevented by 4-PBA or Salubrinal. eIf2α expression was upregulated during ERS and interfering eIf2α expression proportionately down-regulated HGF expression. Inhibition of HGF and c-Met expression was also observed in the ALF rat. Treatment with 4-PBA prevented the reduction of HGF in ALF rats. ER stress regulates HGF expression in vitro and in vivo, which depends on eIf2α pathway. Reduction in liver damage of ALF by 4-PBA is associated with attenuation of ER stress and maintaining HGF production.

Correlation between c-Met and ALDH1 contributes to the survival and tumor-sphere formation of ALDH1 positive breast cancer stem cells and predicts poor clinical outcome in breast cancer

c-Met is a receptor-type tyrosine kinase, which is involved in a wide range of cellular responses such as proliferation, motility, migration and invasion. It has been reported to be overexpressed in various cancers. However, the role of c-Met in breast cancer stem cells (CSCs) still remains unclear. We herein, show that c-Met expression is significantly elevated in Basal-like type of breast cancer in comparison with other subtypes. High expression of c-Met strongly correlated with the expression of two CSC markers, ALDH1A3 and CD133 in breast cancers. In addition, breast cancers at tumor stage III-IV expressing both c-Methigh and ALDH1A3high had poor prognosis. Furthermore, treatment with c-Met inhibitors (Crizotinib, Foretinib, PHA-665752 and Tivantinib) in MDA-MB157 cells with high c-Met protein expression resulted in significant suppression in cell viability, contrary to MDA-MB468 cells with low c-Met protein expression. These c-Met inhibitors also suppressed cell viability and tumor-sphere formation of ALDH1high breast cancer cells with high c-Met expression. These results suggest that c-Met in ALDH1 positive CSCs seems to play an important role in breast cancer repopulation. Therefore, we conclude that c-Met is a potential therapeutic target in ALDH1 positive breast CSCs.

Prognostic value of c-Met overexpression in pancreatic adenocarcinoma: a meta-analysis

The overexpression of c-Met protein has been detected in pancreatic adenocarcinoma (PAC). However, its prognostic impact remains unclear. We performed this meta-analysis to evaluate the prognostic value of c-Met overexpression in PAC. A systematic computerized search of the electronic databases such as PubMed, Embase, and Google Scholar was carried out. From 5 studies, 423 patients who underwent surgical resection for PAC were included in the meta-analysis. Compared with patients with PAC showing low c-Met expression, patients with c-Met-high tumor had significantly worse disease-free survival (hazard ratio = 1.94 [95% confidence interval, 1.46–2.56], P = 0.00001) and overall survival (hazard ratio = 1.86 [95% confidence interval, 1.19–2.91], P = 0.006). In conclusion, this meta-analysis demonstrates that c-Met overexpression is a significant prognostic marker for poor survival in patients who underwent surgical resection for PAC.

Hepatocyte growth factor (HGF) optimizes oral traumatic ulcer healing of mice by reducing inflammation

ObjectiveTo evaluate the influence of overexpression HGF on the healing of traumatic ulcer of oral mucosa of mice. Material and methodsMice were divided into two groups: wild type C57BL6(WT) and HGF high expression transgenic (HGF-Tg) mice. Traumatic ulcer of all mice were made by number 15 scalpel blade. Mice were sacrificed after 5days and the inflammation score and expression of TNFα, IFNγ, c-Met, apoptosis (TUNEL) and 40 serum inflammation cytokines were estimated. ResultsHGF-Tg mice presented a lower inflammation score (p=0.011), Serum TNFα expression in HGF-Tg ulcers is 1.3 times than WT ulcer and the difference is statistical significance (t test, p=0.003). Serum c-Met protein in HGF-Tg mice were significantly higher than WT mice (t test, p=0.004). No statistical difference was observed in the serum IFNγ between WT ulcer and HGF-Tg ulcer (t test, p=0.268). TNFα positive cytoplasm expression cells in connective tissue of HGF-Tg mice is significantly lower than that of WT group (t test, p=0.029). C-Met positive cytoplasm expression cells in both epithelium and connective tissue of HGF-Tg group is significantly higher than that of WT group (t test, p=0.040, p=0.000). Samples in HGF-Tg group showed a lower number of positive cells of epithelium TUNEL staining compared with that in the WT group (t test, p=0.035). ConclusionsHGF exhibited anti-inflammatory potential in oral traumatic ulcer through the reduction of epithelial apoptosis, connective tissue TNFα expression and induction of c-Met expression.