CCR7 expression correlates with subcutaneous involvement in mycosis fungoides skin lesions and promotes migration of mycosis fungoides cells (MyLa) through mTOR activation

Background: The molecular pathogenesis of mycosis fungoides (MF) is currently poorly understood. The chemokine receptor CCR7 has been demonstrated to be involved in the development and progression of certain cancers, but its role in MF has rarely been investigated. Objectives: We seek to determine whether CCR7 is expressed in MF skin lesions. In addition, we evaluate whether CCR7 plays a role in MF cell proliferation and migration, and which signaling pathways are involved. Methods: Immunohistochemical staining of 21 cases of MF pathology specimens with CCR7 was performed. Medical charts and pathology slides of these cases were reviewed. Surface expression of CCR7 on MyLa cells (MF cell line) and peripheral blood mononuclear cells (PBMCs) was assessed by flow cytometry. Cell proliferation and migration were evaluated with the Alamar Blue assay and transwell chemotaxis assay, respectively. Results: CCR7 was found to be expressed in 62% (13 out of 21) of MF pathology specimens, and its expression correlated with subcutaneous extension of lymphoma cells. CCR7 expression was increased on the surface of MyLa cells compared to that on PBMCs. Addition of CCL21 (CCR7 agonist) enhanced MyLa cell migration but not proliferation. The CCL21-induced MyLa cell migration was found to be mediated by the mTOR pathway. Conclusions: CCR7 is more likely to be expressed in MF skin lesions with subcutaneous involvement. Activation of CCR7 promotes migration of MyLa cells (MF cell line) through the mTOR pathway. These findings provide new insights into the significance of CCR7 in the pathophysiology of MF. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.