Integrin β3 and CD44 levels determine the effects of the OPN-a splicing variant on lung cancer cell growth
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Shih-Jung Sun1,*, Chun-Chi Wu1,*, Gwo-Tarng Sheu1, Hui-Yi Chang2, Mei-Yu Chen2, Yu-Ying Lin2, Cheng-Yen Chuang2,3, Shih-Lan Hsu4, Jinghua Tsai Chang1,2,5
1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC
2Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC
3Division of Thoracic Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
4Department of Education & Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
5Department of Chest Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC
*These authors have contributed equally to this study
Jinghua Tsai Chang, email: email@example.com
Keywords: OPN-a, Integrin β3, CD44, NF-kB
Received: November 25, 2015 Accepted: June 07, 2016 Published: July 27, 2016
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.
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