The aim of this study is to assess the effects of the C-1562T polymorphism in the MMP-9 promoter on the risk of occurrence and lymphatic metastasis of non-small cell lung carcinoma (NSCLC).
These findings support the hypothesis that the MMP9-1562 C/T polymorphism is associated with a protective effect against the development of lung cancer and suggest that the MMP2 -735 C/T polymorphism modify the length of survival in NSCLC patients.
The C-1562T, Arg279Gln and Arg668Gln polymorphisms in MMP9 were significantly associated with survival of patients with NSCLC (log-rank p values = 0.032, 0.038 and 0.036, respectively).
Prechemotherapy MMP-9 (ng/ml) levels were significantly higher in patients with advanced stage non-small cell lung cancer than in controls (7.2 ± 2.8 vs 4.5 ± 2.1, P <0.001).
In this study, we performed multivariate analysis of the mRNA levels of 10 selected genes [VEGF-A, VEGF121, VEGF165, VEGF189, S100A4, E-cadherin, Thrombospondin (TSP)-1, TSP-2, matrix metalloproteinase (MMP)-2, and MMP-9] in 130 NSCLC specimens using the real-time quantitative reverse transcription-polymerase chain reaction.
Moreover, our results indicate that angelicin inhibits NSCLC growth not only by downregulating cyclin B1, cyclin E1 and Cdc2, which are related to the cell cycle, but also by reducing MMP2 and MMP9 and increasing E-cadherin expression levels.
Elastin fragments were assessed in serum from patients with stage I-IV non-small cell lung cancer (NSCLC) (n = 40) and healthy controls (n = 30) using competitive ELISAs targeting different protease-generated fragments of elastin: ELM12 (generated by matrix metalloproteinase MMP-9 and -12), ELM7 (MMP-7), EL-NE (neutrophil elastase), EL-CG (cathepsin G) and ELP-3 (proteinase 3).
The data revealed that: i) upregulated miR-768-3p in tumors were associated with the clinicopathological features of NSCLC patients; ii) inhibiting miR-768-3p function by miR-768-3p antagomir induced distinctly apoptosis and Fas/FasL expressional alteration of NSCLC cells; iii) miR-768-3p antagomir transduction also decreased the viability, migration and invasion, as well as MMP-2 and MMP-9 activities in A549 and HCC4006 cells; and iv) miR-768-3p antagomir transfection also inhibited the growth and proliferation of NSCLC xenografts in nude mice.
In summary, tumour-associated neutrophils represent an important source of MMP-9 in NSCLC, and loss of epithelial PTEN may further augment steroid-insensitive expression.
To better understand the role of host MMP9 on the primary growth and metastatic potential of NSCLC, we performed an orthotopic model of NSLC in integrin alpha1-null mice (a genetic model for increased MMP9).
We have recently shown that Semaphorin 4B (SEMA4B) inhibits the invasion of non-small cell lung cancer (NSCLC) through PI3K-dependent suppression of MMP9 activation.
To define the signal transduction cascades downstream of SEMA4b for regulation of MMP9 expression, we inhibited PI3K, ERK/MAPK, or JNK signaling pathway in SEMA4b knockout NSCLC and found that only inhibition of PI3K signaling pathway significantly decreased MMP9 activation.
Our results suggest that MMP-9 is a potential biomarker for NSCLC diagnosis and its combined measurement with other biomarkers could improve NSCLC detection.