Vascular endothelial growth factor-A(165) induces progression of melanoma brain metastases without induction of sprouting angiogenesis.
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-A(165), 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.
Küsters
Benno
B
Department of Pathology, University Medical Centre Nijmegen, 6500 HB Nijmegen, the Netherlands. b.kuesters@pathol.azn.nl
Leenders
William P J
WP
Wesseling
Pieter
P
Smits
Debby
D
Verrijp
Kiek
K
Ruiter
Dirk J
DJ
Peters
Johannes P W
JP
van Der Kogel
Albert J
AJ
de Waal
Robert M W
RM
D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology / Q000556:secondary*; D002455:Cell Division / Q000502:physiology; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A
D016228:Endothelial Growth Factors; D042461:Vascular Endothelial Growth Factor A