These data were further supported by the detection of low vessel density in EGFP-positive regions, as determined by the distribution of intravascularly administered, fluorescence-labeled Lycopersicon esculentum lectin in frozen tumor sections.
In the tumor xenograft studies, VEGFR2 phosphorylation of endothelial cells was not seen, perhaps reflecting low vessel density.
A large fraction of the CAM models exhibited a distinctive phenotype of low vessel density reflecting the dysfunctional angiogenesis which occurs following hypersprouting (Fig. 4a).
When translated into tumour growth, poor delivery due to low vessel density was compensated by high permeability, resulting in a similar growth rate to cords with high vessel density and low permeability.
The hypoxic regions co-localized with avascular regions or regions with very low vessel density, and were found in both central and peripherial parts of sunitinib-treated A-07-GFP tumors.
No data on Vegfa expression are available for this experimental set-up but we can infer from the low vessel density, visualized by PECAM in situ hybridization, that the low Vegfa expression in Fgf9 −/− mutants cannot be rescued by exogenous SHH.
Abundant tumor necrosis with low intratumoral small vessel density is a common feature of distant metastasis.
Factors associated with distant metastasis in the univariate analysis included high tumor budding, low intratumoral small vessel density, absent lymphocyte-containing intratumoral inflammation and abundant necrosis.
A possible explanation for this finding could be an increased fatty acid transportation from the subserosal adipose tissue to the tumor tissue, which had typically a low intratumoral small vessel density and abundant tumor necroses [ 16].
Features associated with distant metastasis in the univariate analysis included high tumor budding (p = 0.002), low intratumoral small vessel density (p = 0.013), absent lymphocellular intratumoral inflammation (p = 0.048) and abundant necrosis (p = 0.073).
