title: Integrin β3 and CD44 levels determine the effects of the OPN-a splicing variant on lung cancer cell growth.
abstract: 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.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Sun
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Gwo-Tarng
authors.initials: GT
authors.lastname: Sheu
authors.affiliation: Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.|Division of Thoracic Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Chuang
authors.affiliation: Department of Education & Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.|Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.|Department of Chest Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC.
authors.forename: Jinghua Tsai
authors.initials: JT
authors.lastname: Chang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis / Q000502:physiology*; D039661:Integrin beta3 / Q000032:analysis / Q000502:physiology*; D008175:Lung Neoplasms / Q000473:pathology*; D016328:NF-kappa B / Q000502:physiology; D053495:Osteopontin / Q000032:analysis / Q000502:physiology*; D012326:RNA Splicing
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C061248:ITGB3 protein, human; D039661:Integrin beta3; D016328:NF-kappa B; C506895:SPP1 protein, human; D053495:Osteopontin
keywords: CD44; NF-kB; OPN-a; integrin β3