Dysregulation of Cytokine Gene Expression as a Cause of T Cell Transformation and In Vivo Tumorigenicity

Abstract

Neoplasia develops due to several molecular perturbations and dysregulation of autocrine growth factor production is one such factor. Recently, we reported that the in vitro spontaneous transformation of a T cell clone resulted exclusively due to constitutive IL-2 autocrine stimulation. However, whether the tumors which originate spontaneously in vivo also use autocrine growth factor stimulation as a mechanism for tumorigenesis is not clear. In the current study, we demonstrate using a murine T cell lymphoma line designated LS A that the tumor growth is dependent on IL-2 autocrine stimulation. The LSA T cell lymphoma line constitutively expressed mRNA for IL-2 and IL-2 receptor β-chain as well as for IL-4 and IL-4 receptors. This cell line was inhibited from growing in vitro in the presence of antibodies against the growth factors or their receptors. Furthermore, the in vivo originated LSA tumor cell line was found to constitutively express immunosuppressive cytokines such as interleukin 10 and TGF-β. Together our data suggest that dysregulation in autocrine growth factor production such as IL-2 and IL-4 can lead to T cell transformation in vivo and furthermore, constitutive production of immunosuppressive cytokines may facilitate the growth of such tumors in vivo.