Vascular endothelial growth factor receptor-3 expression in mycosis fungoides

Abstract

Here, 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.

Keywords::

• Angiogenesis
• VEGF
• VEGF-R
• VEGFR-3
• CTCL

Acknowledgements

We wish to thank Keld Kaltoft (Århus University and CellCure Århus, Denmark) for the generous gift of the MyLa cell lines. The project part concerning establishment and study of CTCL cell lines by Dr. Keld Kaltoft has been approved by “Den videnskabsetiske Kommite i Århus Amt” (The science-ethical committee in Århus County).

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was supported by grants from The University of Copenhagen, The Carlsberg Foundation (Carlsbergfondet), The Danish Cancer Society, The Danish Research Councils, The Novo Nordic Foundation, Dansk Kræftforsknings Fond, The Neye Foundation, The Lundbeck Foundation, The Beckett Foundation, The National Cancer Institute, the Wihlem-Sander-stiftung (C.S.K. and J.C.B.) and the Deutsche Forschungsgemeinschaft (J.C.B.).