Integrin β3 and CD44 levels determine the effects of the OPN-a splicing variant on lung cancer cell growth

Osteopontin (OPN), a phosphorylated glycoprotein, is frequently overexpressed in cancer. Among the three OPN isoforms, OPN-a is the most highly expressed in lung cancer cell lines and lung tumors. Overexpression of OPN-a greatly reduced CL1-5 lung adenocarcinoma cell growth, but had no effect on gro...

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Bibliographic Details
Published in:Oncotarget 2016-08, Vol.7 (34), p.55572-55584
Main Authors: Sun, Shih-Jung, Wu, Chun-Chi, Sheu, Gwo-Tarng, Chang, Hui-Yi, Chen, Mei-Yu, Lin, Yu-Ying, Chuang, Cheng-Yen, Hsu, Shih-Lan, Chang, Jinghua Tsai
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Cell Proliferation
Humans
Hyaluronan Receptors - analysis
Hyaluronan Receptors - physiology
Integrin beta3 - analysis
Integrin beta3 - physiology
Lung Neoplasms - pathology
NF-kappa B - physiology
Osteopontin - analysis
Osteopontin - physiology
Research Paper
RNA Splicing
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Summary:Osteopontin (OPN), a phosphorylated glycoprotein, is frequently overexpressed in cancer. Among the three OPN isoforms, OPN-a is the most highly expressed in lung cancer cell lines and lung tumors. Overexpression of OPN-a greatly reduced CL1-5 lung adenocarcinoma cell growth, but had no effect on growth in A549 lung adenocarcinoma cells. Examination of the expression of integrins and CD44, which are possible OPN-a receptors, revealed that differences in integrin β3 levels might explain this discrepancy between CL1-5 and A549 cells. When integrin β3 was ectopically expressed in A549 cells, OPN-a inhibited their growth, whereas OPN-a increased cell growth following integrin β3 knockdown in CL1-5 cells. This OPN-a-induced increase in growth appeared to result from activation of the CD44/NFκB pathway. Our results demonstrated that OPN-a inhibits growth of cells with high integrin β3 levels and increases growth via activation of the CD44/NFκB pathway in cells with low integrin β3 levels. Thus, OPN-a, integrin β3, and CD44 interact to affect lung cancer cell growth, and this study may aid in the development of cancer treatment strategies involving these molecules.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.10865