Osteopontin splice variants differentially modulate the migratory activity of hepatocellular carcinoma cell lines = 간세포암에서 osteopontin splicing variant의 특이적인 migration기능 차이

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Title
Osteopontin splice variants differentially modulate the migratory activity of hepatocellular carcinoma cell lines = 간세포암에서 osteopontin splicing variant의 특이적인 migration기능 차이
Author(s)
Su Jin Chae; H O Jun; Eun Gyo Lee; S J Yang; Dong Chul Lee; Joon Ki Jung; Kyung Chan ParkYoung Il Yeom; K W Kim
Bibliographic Citation
International Journal of Oncology, vol. 35, no. 6, pp. 1409-1416
Publication Year
2009
Abstract
Osteopontin (OPN, SPP1) is a secretory extracellular matrix protein that has been implicated in cancer-associated mechanisms such as metastasis, invasion and angiogenesis. Three OPN isoforms (OPN-a, -b and -c) derived from alternative splicing are known to exist, but their functional specificity remains unclear. Here, we found that the expression profile of OPN isoforms in hepatocellular carcinoma (HCC) cell lines and patient tissues were correlated with specific cellular phenotypes and tumorigenicity of HCC. Thus, SK-Hep1 cells with a robust migratory capacity dominantly expressed both OPN-a and -b, but non-migratory cell lines such as Hep3B and PLC/PRF/5 mainly expressed OPN-c. Moreover, tumor tissues predominantly expressed OPN-a and -b, whereas normal liver tissues mainly expressed OPN-c. Transwell infiltration and wound-induced migration assays revealed that both OPN-a and -b induced Hep3B cell migration, while OPN-c had no significant effects. By contrast, OPN-c suppressed the migratory activity of SK-Hep1 cells although no significant changes were induced by OPN-a. Consistently, OPN isoforms differentially activated migration-associated signaling pathways such that OPN-a and -b increased the expression of urokinase type plasminogen activator and the phosphorylation of p42/p44 MAP kinase, but these pathways were not activated by OPN-c. Thus, the findings of the present study suggest that OPN splice variants differentially couple to signaling pathways to modulate the migratory property of HCC cells and that this is one of the mechanisms underlying the pathological heterogeneity of HCC progression.
Keyword
Hepatocellular carcinomaMigrationOsteopontinSplice variant
ISSN
1019-6439
Publisher
Spandidos Publ Ltd
DOI
http://dx.doi.org/10.3892/ijo-00000458
Type
Article
Appears in Collections:
Division of Bio Technology Innovation > BioProcess Engineering Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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