Functional characterization of neurotensin receptors in human cutaneous T cell lymphoma malignant lymphocytes

Cutaneous T cell lymphomas are a clonal proliferation of CD4+ T lymphocytes primarily involving the skin. Mycosis fungoides is an epidermotropic CD4cutaneous T cell lymphoma, and a more aggressive form, Sezary syndrome, occ urs when the malignant cells become nonepidermotropic. The role of neuropep tides in the growth and chemotaxis capacity of cutaneous T cell lymphoma ce lls remains unknown. In this report, we found that cutaneous T cell lymphom a cells, similarly to normal resting or activated peripheral lymphocytes, w ere able to bind neurotensin. We used an interleukin-2-dependent cutaneous T cell lymphoma malignant T cell line derived from cutaneous T cell lymphom a lesions in order to study the role of neurotensin in the proliferation an d migration of these malignant cells. First, we determined that the maligna nt cells expressed neurotensin receptors on their cell membrane. Functional results indicated that neurotensin did not stimulate the growth of the cel l line. In contrast, this neuropeptide inhibited the proliferation of the t umor cells in response to exogenous interleukin-2. Furthermore, we found th at neurotensin enhanced both spontaneous and chemoattractant-induced migrat ion of the malignant cells. This suggests that neurotensin in skin can play a role in the disease by locally limiting the growth of the cutaneous T ce ll lymphoma tumor cells in response to cytokines and by enhancing their che motaxis capacity.