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[Cancer Research 62, 341-345, January 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Vascular Endothelial Growth Factor-A165 Induces Progression of Melanoma Brain Metastases without Induction of Sprouting Angiogenesis1

Benno Küsters2,3, William P. J. Leenders2, Pieter Wesseling, Debby Smits, Kiek Verrijp, Dirk J. Ruiter, Johannes P. W. Peters, Albert J. van der Kogel and Robert M. W. de Waal

Departments of Pathology [B. K., W. P. J. L., P. W., K. V., D. J. R., R. M. W. d. W.], Central Animal Laboratory [D. S.], and Radiotherapy [J. P. W. P., A. J. v. d. K.], University Medical Centre Nijmegen, 6500 HB Nijmegen, the Netherlands

We investigated the mechanisms of vascularization in a brain metastases model of malignant melanoma. Parenchymal metastases expressing little vascular endothelial growth factor-A (VEGF-A) co-opted the preexistent brain vasculature, leading to an infiltrative phenotype. Metastases of the human melanoma cell line Mel57, engineered to express recombinant VEGF-A165, showed accelerated growth in a combined expansive and infiltrative pattern with marked central necrosis. This difference in growth profile was accompanied by dilation of co-opted intra- and peritumoral vessels with concomitant induction of vascular permeability. Our data show that modulation of preexistent vasculature can contribute to malignant progression without induction of sprouting angiogenesis.




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