Often described as incomplete or absent, the basement membrane of blood vessels in
tumors has attracted renewed attention as a source of angiogenic and anti-angiogenic molecules, site of
growth factor binding, participant in angiogenesis, and potential target in
cancer therapy. This study evaluated the composition, extent, and structural integrity of the basement membrane on blood vessels in three mouse
tumor models: spontaneous RIP-Tag2 pancreatic islet
tumors, MCa-IV mammary
carcinomas, and Lewis lung
carcinomas.
Tumor vessels were identified by immunohistochemical staining for the endothelial cell markers CD31,
endoglin (CD105),
vascular endothelial growth factor receptor-2, and
integrin alpha5 (CD49e). Confocal microscopic studies revealed that basement membrane identified by
type IV collagen immunoreactivity covered >99.9% of the surface of blood vessels in the three
tumors, just as in normal pancreatic islets.
Laminin,
entactin/
nidogen, and
fibronectin immunoreactivities were similarly ubiquitous on
tumor vessels. Holes in the basement membrane, found by analyzing 1- micro m confocal optical sections, were <2.5 micro m in diameter and involved only 0.03% of the vessel surface. Despite the extensive vessel coverage, the basement membrane had conspicuous structural abnormalities, including a loose association with endothelial cells and pericytes, broad extensions away from the vessel wall, and multiple layers visible by electron microscopy.
Type IV collagen-immunoreactive sleeves were also present on endothelial sprouts, supporting the idea that basement membrane is present where sprouts grow and regress. These findings indicate that basement membrane covers most
tumor vessels but has profound structural abnormalities, consistent with the dynamic nature of endothelial cells and pericytes in
tumors.