title: Interleukin-2 Functions in Anaplastic Large Cell Lymphoma Cells through Augmentation of Extracellular Signal-Regulated Kinases 1/2 Activation.
abstract: In addition to intrinsic genetic alterations, the effects of the extrinsic microenvironment also play a pathological 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 performed 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.
authors.affiliation: Department of Pathology, the Methodist Hospital and the Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.forename: Nianxi
authors.initials: N
authors.lastname: Zhao
authors.forename: Zihua
authors.initials: Z
authors.lastname: Zeng
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhou
authors.forename: Chung-Che
authors.initials: CC
authors.lastname: Chang
authors.forename: Youli
authors.initials: Y
authors.lastname: Zu
keywords: CD25/IL-2 receptor; IL-2 signaling; anaplastic large cell lymphoma (ALCL); extracellular signal-regulated kinases (ERK1/2); tumor microenvironment