Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential.
We studied the relation between tumour vascular density and tumour growth rate, metastatic incidence and vascular permeability factor (VPF) mRNA levels in a human xenograft model described previously. Vascular density was determined by automated image analysis. Xenografts derived from cell lines BLM and MV3 showed the highest mean vascular density (MVD), the highest in vivo growth rate, high VPF mRNA levels and rapid development of lung metastases. Xenografts of cell lines M14, Mel57 and MV1 showed a significantly lower degree of vascularization, lower in vivo growth rates and lower levels of VPF mRNA, but formed lung metastases with a similar incidence as those of BLM and MV3. Xenografts from cell line 1F6 did not form lung metastases, whereas tumours derived from a spontaneous mutant of 1F6, designated 1F6m, gave rise to lung metastases to the same extent as Mel57, M14 and MV1 tumours. MVD values in 1F6 and 1F6m xenografts, VPF mRNA levels and in vivo growth rates of 1F6 and 1 F6m xenografts, however, were similar. In conclusion, in the melanoma xenograft model vascular density is correlated with in vivo growth rate and with in vitro VPF mRNA levels, but not with the ability to metastasize.
Westphal
J R
JR
Department of Pathology, University Hospital Nijmegen, The Netherlands.
van't Hullenaar
R G
RG
van der Laak
J A
JA
Cornelissen
I M
IM
Schalkwijk
L J
LJ
van Muijen
G N
GN
Wesseling
P
P
de Wilde
P C
PC
Ruiter
D J
DJ
de Waal
R M
RM
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008222:Lymphokines / Q000096:biosynthesis*; D008545:Melanoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous / Q000473:pathology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors