4320

MMP11

matrix metallopeptidase 11;MMP11;matrix metallopeptidase 11

MMP-11|matrix metallopeptidase 11 (stromelysin 3)|stromelysin III|stromelysin-3

22q11.23

protein-coding

BACKGROUND: We examined expression patterns of matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in colorectal cancer tissues to assess their prognostic significance. MATERIALS AND METHODS: mRNA expressions of 17 MMPs, 4 TIMPs, and RECK were measured in 112 colorectal cancerous tissues, 20 normal mucosa tissues, and 11 metastatic liver lesions by real-time reverse-transcriptional-polymerase chain reaction. The protein level expressions were confirmed with immunohistochemistry. RESULTS: cancers and normal mucosa displayed highly significant differences (P < 0.01) in expression of nine genes (MMP-1, -3, -7, -9, -10, -11, -12, -14, and RECK). Primary cancers and metastatic lesions showed highly significant differences (P < 0.01) in MMP-1, -10, -11, and TIMP-1. MMP-12 expression was higher in the primary tumors that were associated without hepatic metastasis than those with metastasis (P < 0.01). High expression of MMP-15 was related to longer disease-free survival (generalized Wilcoxon test, P < 0.0062; Cox hazard model, P < 0.028, hazard ratio, 0.099). CONCLUSIONS: MMP, TIMP, RECK expression patterns may provide an insight into extracellular matrix degrading (which is characteristic of colorectal cancers) and its role in metastasis.

BACKGROUND: The aim of the present study was to investigate the association between serum levels of matrix metalloproteinase 11 (MMP-11) and responses to front-line chemotherapy and prognosis in advanced unresectable gastric adenocarcinoma. METHODS: Clinical data concerning 86 patients with advanced gastric adenocarcinoma (stages III c to IV), treated in Beijing Chao-Yang Hospital from 2005 to 2009, were reviewed retrospectively. Adenocarcinoma was confirmed by pathology and patients received 5-fluorouracil-based front-line combination chemotherapy with third generation chemotherapeutic agents including paclitaxel, docetaxel and oxaliplatin. The regimen was repeated every two to three weeks, and the first evaluation was carried out after three cycles. The median cycle of chemotherapy was 6 (ranging from three to twelve cycles). Serum MMP-11 protein from the 86 patients was examined using enzyme-linked-immunosorbent-assay (ELISA) prior to chemotherapy and after three cycles of chemotherapy. Serum samples from healthy individuals were used as controls. RESULTS: The response rate (RR, complete response plus partial response) to chemotherapy in the 86 patients was 44.2% (38/86). The median TTP (time to progression) and overall survival (OS) in patients who responded to chemotherapy were 6.0 and 10.0 months, respectively. The response rate to chemotherapy in patients with high levels of serum MMP-11 (42.9%; 9/21) was similar to that in patients with low levels (44.6%; 29/65) (P = 0.935). Patients with low serum levels of MMP-11 had a higher median survival time and 1-year survival rate than those with high levels (11 months vs. 8 months, 50.2% vs. 21.7%, P = 0.017), although the TTP was comparable in all patients, irrespective of serum MMP-11 level (P = 0.178). Serum MMP-11 levels were correlated with lymph node metastasis (P = 0.006). Cox multivariate regression analysis demonstrated that the serum level of MMP-11 was an independent prognostic factor for patients presenting with advanced gastric carcinoma. CONCLUSIONS: Serum levels of MMP-11 in Chinese patients with advanced gastric carcinoma were not associated with the response to front-line chemotherapy, but could play an important role in lymph node metastasis and prognosis.

OBJECTIVE: To investigate the role of expression of stromelysin-3 in laryngeal carcinoma and the relationship between stromelysin-3 expression and the invasion and metastasis of laryngeal cancer. METHOD: The expression of stromelysin-3 in 63 samples with laryngeal carcinoma and 63 adjacent normal tissue were detected by immunohistochemistry. The mRNA expression of stromelysin-3 were examined by reverse transcript-polymerase chain reaction (RT-PCR) in 22 frozen specimens of laryngeal cancer and 22 adjacent normal tissue. RESULT: The immunochemistry showed the expression of stromelysin-3 in laryngeal cancer is much higher than that in adjacent normal tissue (P < 0.01), RT-PCR showed the expression of stromelysin-3 in laryngeal cancer was much higher than that in adjacent normal tissue (P < 0.01). The expression of stromelysin-3 in protein level was not only much higher in T3 + T4 group than that in T1 + T2 group (P < 0.01) but also much higher in nodal metastases group than that in the group without nodal metastases (P < 0.05). The mRNA expression of stromelysin-3 was higher in T3 +T4 group than that in T1 + T2 group (P < 0.05) and was higher in nodal metastases group than that in group without nodal metastases (P < 0.05). The expression of stromelysin-3 both in protein level and in mRNA level was not associated with different primary location and different histological grade of laryngeal cancer (P > 0.05). CONCLUSION: The expression of stromelysin-3 was closely associated with the invasion and metastases of laryngeal carcinoma, it may be served as a marker in estimating the invasion and metastases potency of laryngeal cancer.

BACKGROUND: Studies have been shown that miR-125a plays an important role in carcinogenesis, however, the role of miR-125a in hepatocellular carcinoma (HCC) remains elusive. METHODOLOGY/PRINCIPAL: Real time-PCR (qRT-PCR) was performed to test the significance of miR-125a in HCC. Ectopic expression of miR-125a was used to test the influences of miR-125a on proliferation and metastasis of HCC cells in vitro and in vivo. Predicted target genes of miR-125a were determined by dual-luciferase reporting, qRT-PCR, and western blot (WB) analyses. Then immunohistochemical staining (IHC) was used to detect the expression of target genes, and the correlations and prognostic values of miR-125a and its target genes were also investigated. CONCLUSIONS/SIGNIFICANCE: Decreased miR-125a was observed in both HCC tissues and cell lines, and associated with patients' aggressive pathologic features. Up-regulating miR-125a significantly inhibited the malignant phenotypes by repressing the expression of matrix metalloproteinase 11 (MMP11) and vascular endothelial growth factor A (VEGF-A) both in vitro and in vivo. Furthermore, miR-125a expression was inversely correlated with both MMP11 and VEGF-A expression in HCC tissues. Inhibiting miR-125a could increase both MMP11 and VEGF-A expression, and RNA interference targeting MMP11 or VEGF-A mRNA could rescue the loss of miR-125a functions. MiR-125a inhibits the proliferation and metastasis of HCC by targeting MMP11 and VEGF-A. Up-regulation of miR-125a might be a promising approach and a prognostic marker for HCC.