Expression and localization of VEGF-C and VEGFR-3 in glioblastomas and haemangioblastomas.
Primary human brain tumours account for approximately 2% of all cancers. High levels of expression of vascular endothelial growth factor-A (VEGF-A), a potent angiogenic factor, are linked to poor prognosis. In contrast, the potential role in human brain tumour biology of newer VEGF family members, VEGF-C and VEGF-D, both of which are lymphangiogenic factors, is poorly understood. In the present study, the expression of all VEGFs (VEGF-A, -B, -C, and -D) and their receptors (VEGFR-1, -2, and -3) has been assessed in 39 primary human brain tumours. The well-established findings were confirmed with VEGF-A. Surprisingly, however, VEGF-C and VEGF-D, as well as VEGFR-3, were expressed in some tumour types such as haemangioblastomas and glioblastomas, despite their lack of lymphatic vessels. VEGF-C and VEGFR-3 transcripts were localized to the tumour palisade around necrotic areas in glioblastomas and were evenly distributed throughout haemangioblastomas. VEGF-C protein was localized by immunohistochemistry to the palisade layer in glioblastomas. More than 50% of VEGF-C-positive cells also expressed the intermediate-stage inflammatory macrophage marker CD163; however, a significant proportion of VEGF-C-positive cells were CD163-negative. These data demonstrate the presence of molecules, primarily described as regulators of lymphangiogenesis, in normal human brain and brain tumours that are devoid of lymphatics. Their localization in macrophages points to a role in tumour-associated inflammation.
Jenny
B
B
Department of Morphology, University Medical Centre, Geneva, Switzerland.
Harrison
J A
JA
Baetens
D
D
Tille
J-C
JC
Burkhardt
K
K
Mottaz
H
H
Kiss
J Z
JZ
Dietrich
P-Y
PY
De Tribolet
N
N
Pizzolato
G P
GP
Pepper
M S
MS
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D001932:Brain Neoplasms / Q000378:metabolism*; D015870:Gene Expression; D005909:Glioblastoma / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D018325:Hemangioblastoma / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D042561:Vascular Endothelial Growth Factor B / Q000096:biosynthesis / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D014408:Biomarkers, Tumor; D006023:Glycoproteins; C119248:LYVE1 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C467484:VEGFA protein, human; C467485:VEGFB protein, human; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D033921:Vesicular Transport Proteins; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3