Quantitative analysis of VEGF-isoforms in head and neck squamous cell carcinoma cell lines: relation to xenotransplantability and tumour progression in mice.
Overexpression of vascular endothelial growth factor (VEGF) is related to tumour progression and xenotransplant-ability in various human solid tumours, but the specific impact of the VEGF-subtypes is still under discussion. The aim of this study was to analyse a possible association of the major VEGF-isoforms and the growth characteristics of xenotransplanted human head and neck squamous cell carcinomas in nude mice. Seven SCC cell lines were analysed by quantitative RT-PCR using the TaqMan-System. We investigated the expression of VEGF-total-mRNA and of the major subtypes VEGF-121, -165, and -189 by using subtype specific primers. The cell lines were xenotransplanted in three mice each, and the data of tumour growth and progression were correlated to the expression of VEGF-isoforms. Six out of the seven cell lines analysed expressed all isoforms of VEGF in different quantities. One cell line expressed generally low levels of VEGF and no VEGF-189 at all. In this cell line xenotransplantation failed in one mice out of three. In a second cell line transplantation also failed in one out of seven mice. Success rates for the other five cell lines were 100%. The cell lines with higher transplantation success were expressed higher VEGF-121/165-189 ratios compared to those without success. In contrast, linearity of tumour growth and lack of necrosis were associated with a lower VEGF-121/165-189 ratio. The findings demonstrate a predominant expression of VEGF-165 and VEGF-189, compared to VEGF-121. We discuss an association of 'growth response rate' measured by tumour growth per detected VEGF-level. In highly proliferating tumours this rate appeared to be about 10 times higher than in low proliferating tumours. We conclude that the ratio between the VEGF-subtypes during tumour implantation and growth is a prerequisite for progression and hypothesise an individual and different response of each tumour cell line to VEGF.
Vlachtsis
Konstantinos
K
Department of Otorhinolaryngology, University Hospital, School of Medicine, Mainz, Germany.
Brieger
Jürgen
J
Kim
Dong-Wook
DW
Gieringer
Rita
R
Hast
Jochem
J
Hengstler
Jan G
JG
Mann
Wolf
W
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002455:Cell Division; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000737:chemistry*; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D008222:Lymphokines / Q000096:biosynthesis* / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors