1. ¹Institute of Pathology and Molecular Pathology, University of Regensburg, University Hospital, Regensburg, Germany
2. ²Institute of Pharmacy, University of Regensburg, Regensburg, Germany
3. ³Department of Hematology and Oncology, University of Regensburg, University Hospital, Regensburg, Germany

Correspondence: Dr A-K Bosserhoff, Institute of Pathology, University of Regensburg, Franz-Josef Strauss Allee 11, D-93053 Regensburg, Germany. E-mail: anja.bosserhoff@klinik.uni-regensburg.de

Received 1 June 2006; Revised 6 October 2006; Accepted 31 October 2006; Published online 18 December 2006.

Abstract

Analyses of malignant melanomas revealed a strong expression of bone morphogenic proteins (BMPs) and their autocrine effect in promoting cell invasion and migration. Here, we report a paracrine effect of BMPs on the vascular network. Both BMP2 and BMP4 induced tube formation as well as the migratory efficiency of microvascular endothelial cells. Melanoma cells with reduced BMP activity attracted less endothelial cells in invasion assays than control cells. Furthermore, reduction of BMPs in melanoma cells had a strong effect on vasculogenic mimicry. Tube formation on matrigel was analysed for melanoma cells as well as in co-cultures of endothelial and melanoma cells. Melanoma cells with reduced BMP activity were not capable of forming cord-like structures by themselves and additionally inhibited tube formation of the endothelial cells. Genes involved in angiogenesis turned out to be strongly downregulated in these cell clones. Tumors derived from cells with impaired BMP activity showed reduced tumor growth or large necrotic areas owing to lack of angiogenesis in in vivo analyses.