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Published on: June 16, 2018
MT2-MMP expression associates with tumor progression and angiogenesis in human lung cancer
Lujun Chen1, Qi Zhou2, Bin Xu1
1Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University Changzhou 213003, Jiangsu, China.
Abstract:
Matrix metalloproteinases (MMPs) are a family of important proteolytic enzymes that play an important role in the remodeling of the tumor microenvironment and associate with tumorigenesis and metastasis. We previously reported that membrane type-2 MMP (MT2-MMP) is highly expressed in human esophageal cancer tissues, and its expression level is positively correlated to tumor size and intratumoral angiogenesis. In order to reveal whether MT2-MMP expression is operative in human lung cancer and its underlying physio-pathological role, in the present study, we examined both mRNA and protein expression levels of MT2-MMP in non-small cell lung caner (NSCLC) tissues and in adjacent normal tissues by using real-time RT-PCR and immunohistochemistry respectively, which showed that both MT2-MMP mRNA (P=0.0359) and protein (P<0.0001) expression levels were significantly increased in cancer tissues in contrast to adjacent normal tissues. Moreover, we also found that the MT2-MMP protein level in cancer tissues positively correlated to lymph node metastasis (P=0.0483), tumor stage (P=0.0483), intra-tumoral microvessel density (MVD) (P=0.0445). We have not found statistically significant correlation between MT2-MMP expression and patients' prognoses, but we found that the patients with both higher MT2-MMP protein expression and higher intra-tumoral microvessel density showed better prognoses than that of the patients with either higher MT2-MMP protein expression or higher intra-tumoral microvessel density (P=0.0311). Thus, our data suggest that MT2-MMP expression positively involves in NSCLC, and might play an important role in promoting the tumor progression and intra-tumoral angiogenesis in NSCLC.
Insights
Matrix metalloproteinase-2 (MT2-MMP) is elevated in non-small cell lung cancer (NSCLC), correlating with tumor progression and angiogenesis. Higher MT2-MMP and microvessel density indicate better patient prognoses.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are key enzymes in tumor microenvironment remodeling, influencing tumorigenesis and metastasis.
- Previous studies indicated high membrane type-2 MMP (MT2-MMP) expression in esophageal cancer, linked to tumor size and angiogenesis.
- The role of MT2-MMP in lung cancer remained to be elucidated.
Purpose of the Study:
- To investigate MT2-MMP expression in non-small cell lung cancer (NSCLC).
- To determine the physio-pathological role of MT2-MMP in NSCLC progression.
- To correlate MT2-MMP levels with clinical parameters and patient prognosis.
Main Methods:
- Real-time RT-PCR was used to quantify MT2-MMP mRNA levels in NSCLC and adjacent normal tissues.
- Immunohistochemistry assessed MT2-MMP protein expression in the same tissue samples.
- Statistical analyses correlated MT2-MMP expression with tumor stage, lymph node metastasis, microvessel density (MVD), and patient prognosis.
Main Results:
- Both MT2-MMP mRNA and protein levels were significantly upregulated in NSCLC tissues compared to normal tissues (P=0.0359 for mRNA, P<0.0001 for protein).
- Higher MT2-MMP protein levels correlated positively with lymph node metastasis (P=0.0483), tumor stage (P=0.0483), and intra-tumoral MVD (P=0.0445).
- While no direct correlation with prognosis was found, combined high MT2-MMP and high MVD predicted better outcomes (P=0.0311).
Conclusions:
- MT2-MMP expression is significantly increased in NSCLC.
- MT2-MMP plays a role in promoting NSCLC progression and intra-tumoral angiogenesis.
- The interplay between MT2-MMP and MVD may influence patient prognosis in NSCLC.
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