Table of Contents
ISRN Oncology
Volume 2011, Article ID 409308, 14 pages
http://dx.doi.org/10.5402/2011/409308
Research Article

Tumor Vascular Morphology Undergoes Dramatic Changes during Outgrowth of B16 Melanoma While Proangiogenic Gene Expression Remains Unchanged

1Medical Biology Section, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
2Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden
3Fifth Medical Department, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
4Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
5Department of Pathology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands

Received 3 August 2011; Accepted 7 September 2011

Academic Editors: S. Mohanam and H. Rizos

Copyright © 2011 Elise Langenkamp et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In established tumors, angiogenic endothelial cells (ECs) coexist next to “quiescent” EC in matured vessels. We hypothesized that angio-gene expression of B16.F10 melanoma would differ depending on the growth stage. Unraveling the spatiotemporal nature thereof is essential for drug regimen design aimed to affect multiple neovascularization stages. We determined the angiogenic phenotype—represented by 52 angio-genes—and vascular morphology of small, intermediate, and large s.c. growing mouse B16.F10 tumors and demonstrated that expression of these genes did not differ between the different growth stages. Yet vascular morphology changed dramatically from small vessels without lumen in small to larger vessels with increased lumen size in intermediate/large tumors. Separate analysis of these vascular morphologies revealed a significant difference in αSMA expression in relation to vessel morphology, while no relation with VEGF, HIF-1α, nor Dll4 expression levels was observed. We conclude that the tumor vasculature remains actively engaged in angiogenesis during B16.F10 melanoma outgrowth and that the major change in tumor vascular morphology does not follow molecular concepts generated in other angiogenesis models.