Clinicopathologic significance of β-catenin and matrix metalloproteinase-2 expression in non-small cell lung cancer

Guang-hu, LI; Cui, Yongsheng; Wu, Qi-Yu; Zhang, Xiong-Ji; Gao, Yufei

doi:10.1007/s12032-012-0437-z

Cited by 9 publications

(12 citation statements)

References 20 publications

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“…The secretion of Shh is more important in H520 squamous cells than in adenocarcinoma A549 cells. In patients, similar results have been reported: Shh expression has been found to be more important in lung squamous carcinoma cells than in lung adenocarcinoma cells [19]. Thus, Shh secretion may be related with the subtype of NSCLC and its intrinsic signaling.…”

Section: Discussionsupporting

confidence: 79%

“…Some studies have described the association between new patterns of gene expression in specific subsets of NSCLC [17], [18], and others suggest the application of new tumor molecular profiling in future therapies. For instance, evaluation of MMP2 and b-catenin expression has been proposed to have a potential in diagnosis of NSCLC with different clinicopathologic characteristics [19]. In SCLC, a tumor with primitive neuroendocrine features, Shh was found to be activated in neuroendocrine progenitor cells and in tumoral cells in mice [20], [21].…”

Section: Introductionmentioning

confidence: 99%

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Gli1 Mediates Lung Cancer Cell Proliferation and Sonic Hedgehog-Dependent Mesenchymal Cell Activation

et al. 2013

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Non-Small-Cell-Lung-Cancer (NSCLC) represents approximately 85% of all lung cancers and remains poorly understood. While signaling pathways operative during organ development, including Sonic Hedgehog (Shh) and associated Gli transcription factors (Gli1-3), have recently been found to be reactivated in NSCLC, their functional role remains unclear. Here, we hypothesized that Shh/Gli1-3 could mediate NSCLC autonomous proliferation and epithelial/stromal signaling in the tumoral tissue. In this context, we have investigated the activity of Shh/Gli1-3 signaling in NSCLC in both, cancer and stromal cells. We report here that inhibition of Shh signaling induces a significant decrease in the proliferation of NSCLC cells. This effect is mediated by Gli1 and Gli2, but not Gli3, through regulation of cyclin D1 and cyclin D2 expression. While exogenous Shh was unable to induce signaling in either A549 lung adenocarcinoma or H520 lung squamous carcinoma cells, both cells were found to secrete Shh ligand, which induced fibroblast proliferation, survival, migration, invasion, and collagen synthesis. Furthermore, Shh secreted by NSCLC mediates the production of proangiogenic and metastatic factors in lung fibroblasts. Our results thus provide evidence that Shh plays an important role in mediating epithelial/mesenchymal crosstalk in NSCLC. While autonomous Gli activity controls NSCLC proliferation, increased Shh expression by NSCLC is associated with fibroblast activation in tumor-associated stroma. Our study highlights the relevance of studying stromal-associated cells in the context of NSCLC regarding new prognosis and therapeutic options.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Gli1 Mediates Lung Cancer Cell Proliferation and Sonic Hedgehog-Dependent Mesenchymal Cell Activation

et al. 2013

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“…Expression of matrix metalloproteinase-9 (MMP-9), a proteinase involved in basement membrane degradation during angiogenesis, is also reported to be involved in tumor invasion and metastasis. Previous studies (Nagakawa et al 2002;Li et al 2009) have demonstrated overexpression of these two markers in various malignancies, and found a possible correlation between their overexpression and lymph node status and clinical staging in cancer. However, there are few studies on MMP-9 and VEGF expression in lung adenocarcinoma and their involvement in tumor invasion and metastasis.…”

Section: Introductionmentioning

confidence: 87%

“…Negative controls for non-specific staining were done on tissue sections using pre-immune serum IgG in place of primary antibodies while positive controls were done on specimens known to express specific antigens. The results were evaluated using the methods of Li et al (2009). Tissues scored between 0 and 1 were classified as low expression and tissues with a score ≥2 were classified as high expression.…”

Section: Cell Linesmentioning

confidence: 99%

Correlation between matrix metalloproteinase-9 and vascular endothelial growth factor expression in lung adenocarcinoma

Wen

2015

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the correlation between the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) and clinicopathological features of lung adenocarcinoma. The expression of MMP-9 and VEGF was evaluated by immunohistochemistry of 30 samples from lung adenocarcinoma patients and 12 paratumoral (normal) tissue samples. In addition, the change in VEGF or MMP-9 expression after MMP-9 or VEGF blockade, respectively, was measured using western blot in lung adenocarcinoma A549 cells. High expression of MMP-9 was found in 63.3% of adenocarcinoma tissues versus 16.7% in normal tissues (P < 0.05). High expression of VEGF was found in 70% of adenocarcinoma tissues versus 25% in normal tissues (P < 0.05). A positive correlation was identified between MMP-9 and VEGF expression (correlation coefficient = 0.7094, P < 0.001), and their mutual overexpression was associated with clinical staging and lymph node status (P < 0.05). In addition, an decrease in VEGF protein expression was observed after MMP-9 blockade by an MMP-9-specific monoclonal antibody. Similarly, a decrease in MMP-9 protein expression was found after VEGF blockade by 19343 MMP-9 and VEGF in lung adenocarcinoma ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 19342-19348 (2015) a VEGF-specific monoclonal antibody. In conclusion, VEGF and MMP-9 are overexpressed in lung adenocarcinoma tissues, and they have a synergistic effect on the invasion and metastasis of adenocarcinoma.

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“…MMP-2 degrades type IV collagen within basement membranes, which are the primary barrier to cancer invasion (6). Previous studies have reported a role for MMP-2 in the invasion of pancreatic, ovarian and lung cancer (7–9). However, the function of MMP-2 in esophageal carcinoma remains uncertain.…”

Section: Introductionmentioning

confidence: 97%

Effects of RNA silencing of matrix metalloproteinase-2 on the growth of esophageal carcinoma cells in vivo

Shen

Feng

et al. 2016

Oncology Letters

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Esophageal carcinoma is one of the most common malignancies in China. Previous studies reported that matrix metalloproteinases (MMPs) have important roles in the progression and invasion of numerous types of solid tumors. Among the MMPs, MMP-2 has been closely associated with tumor growth and invasion. In the present study, a short hairpin RNA (shRNA) lentiviral expression vector targeting the MMP-2 gene was constructed in order to observe the inhibitory effect of MMP-2 gene silencing on the growth of the KYSE150 esophageal carcinoma cell line in vivo. Three small hairpin RNA sequences targeting MMP-2 were designed and cloned into lentiviral vectors. Following transfection of the lentiviral vectors into KTSE150 cells, MMP-2 mRNA and protein expression levels were examined by reverse transcription-quantitative polymerase chain reaction and western blotting, and the growth rate of cells was analyzed by MTT assays. Subsequently, tumor growth was assessed in nude mice. Lentivirus-mediated RNA interference effectively inhibited the expression of MMP-2 mRNA and protein in KYSE150 esophageal carcinoma cells, and suppressed the growth of esophageal carcinoma cells in vivo. The results of the present study suggested that lentivirus-mediated gene therapy targeting MMP-2 may be an attractive strategy for the treatment of esophageal carcinoma and justifies the performance of further studies on the application of lentivirus vectors to cancer gene therapy.

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Clinicopathologic significance of β-catenin and matrix metalloproteinase-2 expression in non-small cell lung cancer

Cited by 9 publications

References 20 publications

Gli1 Mediates Lung Cancer Cell Proliferation and Sonic Hedgehog-Dependent Mesenchymal Cell Activation

Gli1 Mediates Lung Cancer Cell Proliferation and Sonic Hedgehog-Dependent Mesenchymal Cell Activation

Correlation between matrix metalloproteinase-9 and vascular endothelial growth factor expression in lung adenocarcinoma

Effects of RNA silencing of matrix metalloproteinase-2 on the growth of esophageal carcinoma cells in vivo

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