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Influence of up-regulation of Notch ligand DLL4 on biological behaviors of human gastric cancer cells.
- Source :
-
World journal of gastroenterology [World J Gastroenterol] 2013 Jul 28; Vol. 19 (28), pp. 4486-94. - Publication Year :
- 2013
-
Abstract
- Aim: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms.<br />Methods: A recombinant eukaryotic expression vector containing human DLL4 gene was constructed and transfected into the human gastric cancer cell line SGC7901. Clones with up-regulated DLL4 were selected and amplified. The effect of DLL4 up-regulation on gastric cancer cell growth was assessed using cell growth assay. The migration and invasion were assessed using a transwell migration assay and matrigel invasion assay. Matrix metalloproteinases were detected using the zymogram technique. Cells were implanted subcutaneously into male BALB/c nu/nu mice. Tumor volumes were then calculated and compared. DLL4 staining in the implanted tumor was performed using immunohistochemistry technique.<br />Results: Growth curves over a six-day time course showed significantly promoted cell proliferation of SGC7901 cells with up-regulated DLL4. DLL4 up-regulation in SGC7901 cells promoted the migration (205.4 ± 15.2 vs 22.3 ± 12.1, P < 0.05) and invasion (68.8 ± 5.3 vs 18.2 ± 6.0, P < 0.05) in vitro and tumorigenicity in vivo (2640.5 ± 923.6 mm(3) vs 1115.1 ± 223.8 mm(3), P < 0.05). Furthermore, significantly increased mRNA level and increased secretion of matrix metalloproteinase-2 (MMP-2) proenzyme were observed in SGC7901 cells with up-regulated DLL4. However, increased MMP-9 mRNA level but decreased extracellular MMP-9 proenzyme level was observed.<br />Conclusion: Our observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.
- Subjects :
- Adaptor Proteins, Signal Transducing
Animals
Calcium-Binding Proteins
Cell Line, Tumor
Cell Movement
Cell Proliferation
Gene Expression Regulation, Neoplastic
Humans
Intercellular Signaling Peptides and Proteins genetics
Ligands
Male
Matrix Metalloproteinase 2 metabolism
Matrix Metalloproteinase 9 metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Signal Transduction
Stomach Neoplasms genetics
Stomach Neoplasms pathology
Time Factors
Transfection
Tumor Burden
Up-Regulation
Intercellular Signaling Peptides and Proteins metabolism
Receptors, Notch metabolism
Stomach Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2219-2840
- Volume :
- 19
- Issue :
- 28
- Database :
- MEDLINE
- Journal :
- World journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 23901223
- Full Text :
- https://doi.org/10.3748/wjg.v19.i28.4486