Functional and structural characteristics of tumor angiogenesis in lung cancers overexpressing different VEGF isoforms assessed by DCE- and SSCE-MRI
Journal
PLoS ONE
Journal Volume
6
Journal Issue
1
Pages
e16062
Date Issued
2011
Author(s)
Lin C.-Y.
Chou C.-H.
Shih C.-M.
Chen C.-Y.
Cheng H.-W.
Chen Y.-F.
Chen J.J.W.
Chen J.-H.
Abstract
The expressions of different vascular endothelial growth factor (VEGF) isoforms are associated with the degree of tumor invasiveness and the patient's prognosis in human cancers. We hypothesized that different VEGF isoforms can exert different effects on the functional and structural characteristics of tumor angiogenesis. We used dynamic contrast-enhanced MRI (DCE-MRI) and steady-state contrast-enhanced MRI (SSCE-MRI) to evaluate in vivo vascular functions (e.g., perfusion and permeability) and structural characteristics (e.g., vascular size and vessel density) of the tumor angiogenesis induced by different VEGF isoforms (VEGF121, VEGF165, and VEGF189) in a murine xenograft model of human lung cancer. Tumors overexpressing VEGF189 were larger than those overexpressing the other two VEGF isoforms. The Ktrans map obtained from DCE-MRI revealed that the perfusion and permeability functions of tumor microvessels was highest in both the rim and core regions of VEGF189-overexpressing tumors (p<0.001 for both tumor rim and core). The relative vessel density and relative vessel size indexes derived from SSCE-MRI revealed that VEGF189-overexpressing tumors had the smallest (p<0.05) and the most-dense (p<0.01) microvessels, which penetrated deeply from the tumor rim into the core, followed by the VEGF165- overepxressing tumor, whose microvessels were located mainly in the tumor rim. The lowest-density microvessels were found in the VEGF121-overexpressing tumor; these microvessels had a relatively large lumen and were found mainly in the tumor rim. We conclude that among the three VEGF isoforms evaluated, VEGF189 induces the most densely sprouting and smallest tumor microvessels with the highest in vivo perfusion and permeability functions. These characteristics of tumor microvessels may contribute to the reported adverse effects of VEGF189 overexpression on tumor progression, metastasis, and patient survival in several human cancers, including non-small cell lung cancer, and suggest that applying aggressive therapy may be necessary in human cancers in which VEGF189 is overexpressed. ? 2011 Yuan et al.
SDGs
Other Subjects
unclassified drug; vasculotropin; vasculotropin 121; vasculotropin 165; vasculotropin 189; contrast medium; isoprotein; vasculotropin A; animal cell; animal experiment; animal model; article; cancer survival; contrast enhancement; controlled study; human; human cell; immunohistochemistry; lung cancer; lung carcinogenesis; lung non small cell cancer; male; microvasculature; mouse; nonhuman; nuclear magnetic resonance imaging; nucleotide sequence; perfusion; permeability; protein expression; steady state; tumor growth; tumor vascularization; tumor volume; animal; cancer transplantation; gene expression regulation; genetics; lung tumor; methodology; neovascularization (pathology); nuclear magnetic resonance imaging; pathology; prognosis; vascularization; xenograft; Murinae; Animals; Contrast Media; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Mice; Neoplasm Transplantation; Neovascularization, Pathologic; Prognosis; Protein Isoforms; Transplantation, Heterologous; Vascular Endothelial Growth Factor A
Type
journal article