Vascular endothelial growth factor receptor-3 expression in mycosis fungoides

Ida Holst Pedersena, Andreas Willerslev-Olsena, Claudia Vetter-Kauczokb, Thorbjørn Krejsgaarda, Britt Lauenborga, Katharina Luise Koppa, Carsten Geislera, Charlotte M. Bonefelda, Qian Zhangc, Mariusz A. Wasikc, Sally Dabelsteend, Anders Woetmanna, Jurgen C. Beckere & Niels Odum*aa epartment of International Health, Immunology and Microbiology, University of Copenhagen, Denmarkb Department of Dermatology, Julius-Maximilians-University, Würzburg, Germanyc Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USAd Department of Oral Medicine, Pathology and Anatomy, School of Dentistry, University of Copenhagen, Denmarke Department of Dermatology, University of Graz, Austria*These authors contributed equally to this work.Correspondence: Niels Odum, Department of International Health, Immunology and Microbiology, Panum Institute 22.5.28, University of Copenhagen, Blegdamsvej 3c, DK2200 Copenhagen N, Denmark. Tel: +4535327879; Fax: +4535327863. E-mail: ndum@sund.ku.dkAbstractHere, we have studied vascular endothelial growth factor receptor-3 (VEGFR-3) expression in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL). Immunohistochemistry revealed that in two-thirds of 34 patients, VEGFR-3 was expressed in situ by both tumor and stromal cells irrespective of the disease stage. The natural VEGFR-3 ligand, VEGF-C, partially protected malignant T-cell lines from growth inhibition by the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA). Whereas the malignant T cells did not produce VEGF-C in vitro, its expression was induced during tumor formation in vivo in a xenograft mouse model of MF. In conclusion, malignant and stromal cells express high levels of VEGFR-3 in all stages of MF. Moreover, malignant T cells trigger enhanced VEGF-C expression in fibroblasts, suggesting that cross-talk between tumor and stromal cells plays a role in lymphangiogenesis and possibly disease progression.