東邦大学 教育・研究業績データベース   
     


  イトウ マサノリ   Ito Masanori
  伊藤 雅方
   所属   東邦大学  医学部 医学科
   職種   講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Interleukin-2 Functions in Anaplastic Large Cell Lymphoma Cells through Augmentation of Extracellular Signal-Regulated Kinases 1/2 Activation
掲載誌名 正式名:InternatIonal journal of BIomedIcal scIence
略  称:Int J BIomed ScI
ISSNコード:1550-9702
インパクトファクター 1.98
巻・号・頁 7(3),181-190頁
著者・共著者 Ito M, Zhao N, Zeng Z, Zhou X, Chang CC, Zu Y
発行年月 2011/09
概要 In addition to intrinsic genetic alterations, the effects of the extrinsic microenvironment also play a patho- logical role in cancer development. Altered chemokine/cytokine networks in the tumor microenvironment may contribute to the dysregulation of cellular functions in cancer cells. Anaplastic large cell lymphoma (ALcL) is an aggressive t-cell lymphoma caused by abnormal expression of anaplastic lymphoma kinase due to a chromosomal translocation. Notably, ALcL cells are also characterized by high-level expression of the high- affinity IL-2 receptor subunit CD25 on the cell surface. However, whether the IL-2/IL-2 receptor functions in ALcL cells and how this signaling affects the tumor remain unclear. In this study, we treated cultured ALcL cells with exogenous IL-2 and examined changes in cellular function and signaling pathways. IL-2 stimulated cell growth and augmented activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway. Additionally, IL-2 enhanced lymphoma cell survival by overcoming kinase inhibitor U0126-induced growth arrest and apoptosis. Subsequently, to identify the potential source of IL-2 for lymphoma cells in vivo, we per- formed gene expression and immunochemical analyses. RT-PCR revealed no IL-2 gene expression in cultured ALCL cells and ruled out the possibility of an IL-2 autocrine loop. Interestingly, immunostaining of lymphoma tumor tissues showed IL-2 protein expression in background cells within tumor tissue, but not in ALCL cells. Our findings demonstrate that IL-2 signaling plays a functional role in ALCL cells, and enhances lymphoma cell survival by increasing activation of the ERK1/2 pathway.