Overexpression of Ang-1 in human gastric cancer cells promotes cell adhesion, invasion, and migration by upregulating integrin beta1, CD44V6, uPA, and MMP-2.
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May promote gastric cancer invasiveness in preclinical models; leaves open therapeutic targeting in patients.
AIM: To evaluate the effects of angiopoietin-1 (Ang-1) on adhesion of gastric cancer cell line BGC-823 and expression of integrin beta1, CD44V6, urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-2 (MMP-2). METHODS: BGC-823 cells were transfected transiently with adenovirus-Ang-1 (Ad-Ang-1). Cells transfected transiently with adenovirus-green fluorescent protein (Ad-GFP) and untransfected cells were used as a negative and blank control group, respectively. The cell adhesion rate between cell and extracellular matrix (ECM) was determined by cell adhesion assay. To investigate whether Ang-1 could reinforce gastric carcinoma metastasis, we performed migration and invasion assays in BGC-823 cells. The mRNA and protein expression of integrin beta1, CD44V6, uPA and MMP-2 were detected by reverse transcription polymerase chain reaction and Western blotting, respectively. The expression of integrin beta1 and CD44V6 was measured by immunohistochemistry. RESULTS: BGC-823 cells were transfected successfully. The adhesion rate increased significantly in the Ad-Ang-1 group (P < 0.05). The Ad-Ang-1-transfected group had a significant increase in migration and invasion compared with that of the mock-transfected and Ad-GFP groups. The mRNA and protein expression of integrin beta1, CD44V6, uPA and MMP-2 in the Ad-Ang-1 group was higher than that in the Ad-GFP and blank control groups (P < 0.05). Compared with mock-transfected and Ad-GFP groups, integrin beta1 and CD44V6 expression intensity greatly increased (P < 0.05). CONCLUSION: Transfection of Ang-1 into human gastric cancer cell line BGC-823 can significantly increase expression of integrin beta1 and CD44V6, by which cell adhesion and metastasis to the ECM are promoted.
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Ou et al. (2009) studied this question.
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