Expression dynamics of CXCL12 and CXCR4 during the progression of mycosis fungoides. (5th September 2014)

• Record Type: Journal Article
• Authors: Daggett, R.N.; Kurata, M.; Abe, S.; Onishi, I.; Miura, K.; Sawada, Y.; Tanizawa, T.; Kitagawa, M.
• Is Part Of: British journal of dermatology. Volume 171:Number 4(2014:Oct.)
• Page Start: 722
• Page End: 731
• Publication Date: 2014-09-05
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.13054
• Languages: English
• ISSNs: 0007-0963

Abstract

<abstract abstract-type="main" id="bjd13054-abs-0001"> <title>Summary</title> <sec id="bjd13054-sec-0001" sec-type="section"> <title>Background</title> <p>Mycosis fungoides (MF) classically presents from patch stage to plaque stage over a number of years and finally progresses to tumour stage with nodal or visceral involvement. The mechanism of progression remains incompletely elucidated. Chemokines and their receptors are known to be involved in disease mechanisms, with CXCL12 and CXCR4 playing a critical role in carcinogenesis, invasion and cancer cell migration in various carcinomas.</p> </sec> <sec id="bjd13054-sec-0002" sec-type="section"> <title>Objectives</title> <p>To investigate the expression of CXCL12 and CXCR4 in different cutaneous stages of MF.</p> </sec> <sec id="bjd13054-sec-0003" sec-type="section"> <title>Methods</title> <p>Formalin‐fixed, paraffin‐embedded skin samples from 40 patients with MF (21 patch stage, 10 plaque stage, nine tumour stage) and 30 non‐neoplastic control skin samples were analysed. CXCL12 and CXCR4 were assessed by quantitative reverse‐transcription polymerase chain reaction and immunohistochemical staining.</p> </sec> <sec id="bjd13054-sec-0004" sec-type="section"> <title>Results</title> <p>The expression level of mRNA for <italic>CXCL12</italic> in plaque‐stage MF was significantly higher than in control skin (<italic>P </italic>=<italic> </italic>0·0035), or patch‐stage (<italic>P </italic>=<italic> </italic>0·0108) or tumour‐stage disease (<italic>P </italic>=<italic> </italic>0·0089). The <italic>CXCR4 </italic>mRNA expression level in plaque‐stage disease was significantly higher than in control skin (<italic>P </italic>=<italic> </italic>0·0090) or patch‐stage disease (<italic>P </italic>=<italic> </italic>0·0387). CXCL12‐ and CXCR4‐positive cell rates in patch‐stage and plaque‐stage MF were significantly higher than those in control skin (<italic>P</italic> < 0·0001). CXCL12‐ and CXCR4‐positve cell rates in tumour‐stage MF were significantly lower than those in patch‐ and plaque‐stage disease (<italic>P </italic>=<italic> </italic>0·0274 and <italic>P </italic>=<italic> </italic>0·0492, respectively).</p> </sec> <sec id="bjd13054-sec-0005" sec-type="section"> <title>Conclusions</title> <p>Our data suggest that neoplastic T cells in MF are exposed to the microenvironment, given the abundance of CXCL12 during its progression, and also that neoplastic T cells express CXCR4, especially in the pretumour stage. We reveal that the CXCL12–CXCR4 axis plays a critical role in MF progression.</p> </sec> </abstract>