CD147-Cyclophilin a Interactions Promote Proliferation and Survival of Cutaneous T-Cell Lymphoma.

Minami Sakamoto,Naomi Takahashi-Shishido,Tomomitsu Miyagaki,Hiroaki Kamijo,Hiraku Suga,Makoto Sugaya,Tomonori Oka,Hikari Boki,Shinichi Sato

doi:10.3390/ijms22157889

Abstract

CD147, a transmembrane glycoprotein that belongs to the immunoglobulin superfamily, and cyclophilin A (CypA), one of the binding partners of CD147, are overexpressed in tumor cells and associated with the progression of several malignancies, including both solid and hematological malignancies. However, CD147 and CypA involvement in cutaneous T-cell lymphoma (CTCL) has not been reported. In this study, we examined CD147 and CypA expression and function using clinical samples of mycosis fungoides (MF) and Sézary syndrome (SS) and CTCL cell lines. CD147 and CypA were overexpressed by tumor cells of MF/SS, and CypA was also expressed by epidermal keratinocytes in MF/SS lesional skin. Serum CypA levels were increased and correlated with disease severity markers in MF/SS patients. Anti-CD147 antibody and/or anti-CypA antibody suppressed the proliferation of CTCL cell lines, both in vitro and in vivo, via downregulation of phosphorylated extracellular-regulated kinase 1/2 and Akt. These results suggest that CD147-CypA interactions can contribute to the proliferation of MF/SS tumor cells in both a autocrine and paracrine manner, and that the disruption of CD147-CypA interactions could be a new therapeutic strategy for the treatment of MF/SS.

Highlights

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL) and typically presents in the form of skin patches and/or plaques, which can occasionally progress to skin tumors, with subsequent lymph node and rarely visceral organ involvement [1,2]
To assess CD147 expression on tumor cells of CTCL, we investigated CD147 expression on peripheral blood mononuclear cells (PBMCs) from Sézary syndrome (SS) patients and normal controls by flow cytometry
The efficacy of T and NK cells transduced with a chimeric antigen receptor (CAR) that recognizes CD147 has been demonstrated in hepatocellular carcinoma (HCC) using xenograft mouse models [33]

Summary

Introduction

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL) and typically presents in the form of skin patches and/or plaques, which can occasionally progress to skin tumors, with subsequent lymph node and rarely visceral organ involvement [1,2]. A variety of systemic therapies are currently available, there are no curative options for such patients, except for stem cell transplantation, and the treatment of advanced MF and SS still remains challenging [2,5,6]. Cell to cell interactions between tumor cells through surface molecules and soluble factors contribute to survival and regulate malignant growth in the form of autocrine or paracrine loops in CTCL [7,8,9,10,11]

Methods

Results

Conclusion