Interleukin-2 functions in anaplastic large cell lymphoma cells through augmentation of extracellular signal-regulated kinases 1/2 activation

Masanori Ito, Nianxi Zhao, Zihua Zeng, Xiaobo Zhou, Chung Che Chang, Youli Zu

Research output: Contribution to journalArticle

5 Scopus citations

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 highaffinity 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.

Original languageEnglish (US)
Pages (from-to)181-190
Number of pages10
JournalInternational Journal of Biomedical Science
Volume7
Issue number3
StatePublished - Sep 15 2011

Keywords

  • Anaplastic large cell lymphoma (ALCL)
  • CD25/IL-2 receptor
  • Extracellular signal-regulated kinases (ERK1/2)
  • IL-2 signaling
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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