Detection of matrix metalloproteinase activity in human pancreatic cancer

Koshiba, Takatomo; Hosotani, Ryo; Wada, Michihiko; Fujimoto, Koji; Lee, Jeon-Uk; Doi, Ryuichiro; Arii, Shigeki; Imamura, Masayuki

doi:10.1007/bf00941802

Cited by 40 publications

(24 citation statements)

References 4 publications

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“…Using higher concentrations of SDF-1a (25 mM), a downregulation of the response was observed, which is probably due to CXCR4 downregulation [Koshiba et al, 1997]. LRRC4 could inhibit the SDF-1a-induced proliferation in U251/LRRC4 cells, compared with that in U251/mock cells (P < 0.01).…”

Section: Resultsmentioning

confidence: 72%

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LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP‐2 activation by reducing SDF‐1α/CXCR4‐mediated ERK1/2 and Akt signaling pathways

Chen

et al. 2007

J of Cellular Biochemistry

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Gliomas take a number of different genetic routes in the progression to glioblastoma multiforme, a highly invasive variant that is mostly unresponsive to current therapies. The alpha-chemokine stromal cell-derived factor (SDF)-1 alpha binds to the seven transmembrane G-protein-coupled CXCR-4 receptor and acts to modulate cell migration and proliferation by activating multiple signal transduction pathways. Leucine-rich repeats containing 4 (LRRC4), a putative glioma suppressive gene, inhibits glioblastoma cells tumorigenesis in vivo and cell proliferation and invasion in vitro. We also previously demonstrated that LRRC4 controlled glioblastoma cells proliferation by ERK/AKT/NF-kappa B signaling pathway. In the present study, we demonstrate that CXC chemokine receptor 4 (CXCR4) is expressed in human glioblastoma U251 cell line, and that SDF-1 alpha increases the proliferation, chemotaxis, and invasion in CXCR4+ glioblastoma U251 cells through the activation of ERK1/2 and Akt. The reintroduction of LRRC4 in U251 cells inhibits the expression of CXCR4 and SDF-1 alpha/CXCR4 axis-mediated downstream intracellular pathways such as ERK1/2 and Akt leading to proliferate, chemotactic and invasive effects. Furthermore, we provide evidence for proMMP-2 activation involvement in the SDF-1 alpha/CXCR4 axis-mediated signaling pathway. LRRC4 significantly inhibits proMMP-2 activation by SDF-1 alpha/CXCR4 axis-mediated ERK1/2 and Akt signaling pathway. Collectively, these results suggest a possible important "cross-talk" between LRRC4 and SDF-1 alpha/CXCR4 axis-mediated intracellular pathways that can link signals of cell proliferation, chemotaxis and invasion in glioblastoma, and may represent a new target for development of new therapeutic strategies in glioma.

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Section: Resultsmentioning

confidence: 72%

“…To determine the relative concentration and activity of gelatinases in the conditioned medium, SDS-PAGE gelatin zymography was performed by using a previously reported method [Koshiba et al, 1997]. Briefly, 40 ml of each conditioned medium was treated with SDS-PAGE sample buffer without boiling and reduction.…”

Section: Gelatin Zymographymentioning

confidence: 99%

LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP‐2 activation by reducing SDF‐1α/CXCR4‐mediated ERK1/2 and Akt signaling pathways

Chen

et al. 2007

J of Cellular Biochemistry

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“…MMP-2 expression is enhanced in pancreatic cancer in cells at the invasive front rather than in the tumor center [18]. Although MMP-2 expression in pancreatic cancer has been investigated in several studies by various methods, the prognostic role of MMP-2 yet has to be fully elucidated [16, 17,19,20,21]. The aim of this study was to evaluate the expression of MMP-2 and its prognostic value in 127 pancreatic ductal adenocarcinomas.…”

Section: Introductionmentioning

confidence: 99%

Epithelial MMP-2 Expression Correlates with Worse Prognosis in Pancreatic Cancer

et al. 2006

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Objective: Matrix metalloproteinases (MMPs) degrade extracellular matrix and are involved in tumor invasion and metastasis in various cancers. In pancreatic cancer, MMP-2 expression is upregulated and correlates with tumor recurrence. The aim of this study was to evaluate the prognostic significance of MMP-2 in pancreatic ductal adenocarcinoma. Methods: MMP-2 expression was assessed by immunohistochemistry in 127 patients operated on at Helsinki University Hospital from 1974 to 1998, with expression interpreted separately in epithelial and stromal samples. Results: Epithelial MMP-2 expression was strong in 5%, moderate in 20%, weak in 25% and negative in 50% of the tumors, with high epithelial MMP-2 expression significantly associated in univariate survival analysis with advanced stage, poor grade and poor survival. Stromal MMP-2 expression was strong in 0%, moderate in 14%, weak in 70% and negative in 16% of the cases, and did not significantly correlate with patient survival. Conclusion: Epithelial MMP-2 correlates with advanced tumor stage and grade, but is not an independent predictor of survival.

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“…MMPs are a group of calcium-and zinc-dependent proteases, and together with their inhibitor, tissue inhibitor of metalloproteinases (TIMPs), regulate tumor invasion and metastasis. Among them, MMP-2 and MMP-9 were found to be overexpressed in pancreatic cancer tissue and closely associated with tumor invasion and metastasis (8,9). In addition, Farrow et al (10) reported that the selective PPARγ agonist RGZ enhanced the expression of phosphatase and tensin homolog (PTEN) in pancreatic cancer AsPC-1 cells and inhibited AKT phosphorylation, while application of the PPARγ inhibitor GW9662 suppressed PTEN expression, suggesting that PPARγ ligands attenuate pancreatic cancer cell growth via inhibiting phosphoinositide 3-kinase (PI3K) activity through upregulating the expression of the tumor suppressor gene PTEN.…”

Section: Introductionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor-γ inhibits pancreatic cancer cell invasion and metastasis via regulating MMP-2 expression through PTEN

Zhang

Lin

et al. 2015

Molecular Medicine Reports

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Abstract. The invasive and metastatic behavior of pancreatic cancer is associated with a poor prognosis. Therefore, understanding the molecular mechanisms underlying the invasion and metastasis of pancreatic cancer has important application values theoretically and clinically. In previous years, with increasing studies focusing on tumor pathogenesis, it has been revealed that peroxisome proliferator-activated receptor-γ (PPARγ) and phosphatase and tensin homolog (PTEN) are closely associated with the occurrence and development of pancreatic cancer. Thus, in the present study, a scratch wound assay, western blotting and transwell assays were used to investigate their function. The scratch wound assay demonstrated that treatment with the PPARγ ligand rosiglitazone (RGZ) could reduce the movement and migration of pancreatic cancer cells. Western blotting results indicated that while RGZ inhibited the expression of matrix metalloproteinase (MMP)-2, PPARγ inhibitors promoted MMP-2 expression. However, PPARγ ligands and inhibitors did not affect the expression of MMP-9. Further investigation indicated that the regulation of MMP-2 by PPARγ activation occurred through PTEN. In addition, PPARγ activation promoted PTEN expression, thereby inhibiting the expression of MMP-2. Subsequent transwell experiments demonstrated that RGZ treatment significantly inhibited the invasiveness of pancreatic cancer cells and the inhibitory effect of RGZ was completely reversed by simultaneous transfection of the MMP-2-overexpressing vector, which increased the invasiveness of pancreatic cancer cells. Therefore, PPARγ activation can activate PTEN expression, thereby suppressing the expression of MMP-2 and hence inhibiting the invasion and metastasis of pancreatic cancer cells.

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Detection of matrix metalloproteinase activity in human pancreatic cancer

Cited by 40 publications

References 4 publications

LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP‐2 activation by reducing SDF‐1α/CXCR4‐mediated ERK1/2 and Akt signaling pathways

LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP‐2 activation by reducing SDF‐1α/CXCR4‐mediated ERK1/2 and Akt signaling pathways

Epithelial MMP-2 Expression Correlates with Worse Prognosis in Pancreatic Cancer

Peroxisome proliferator-activated receptor-γ inhibits pancreatic cancer cell invasion and metastasis via regulating MMP-2 expression through PTEN

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