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.