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KMID : 0616620030090020115
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Journal of Soonchunhyang Medical College
2003 Volume.9 No. 2 p.115 ~ p.121
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Quantitative analysis of VEGF-isoforms in head and neck squamous cell carcinoma cell lines
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Kim Dong-Wook
Lee Jong-Dae
Park Jin-Kyu
Lee Jae-Hyung
Lee Byung-Don
Chang Hyuk-Soon
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Abstract
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Overexpression of vascular endothelial growth factor(VEGF) is related to tumor progression and xenotransplantability in various human solid tumors, 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 carcinoma tumors in nude mice. Seven squamous cell carcinoma cell lines were analysed by quantitative RT-PCR using the Taqman^(TM)-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 tumor growth and progression were correlated to the expression of VEGF-isoforms. We also investigated an "growth response rate" measured by tumor growth per detected VEGF-level. 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 failed in one out of seven mice, too. Success rates for the other five cell lines were 100%. The cell lines with higher transplantation success were expressing higher VEGF-121/165-189 ratios comparing to those without success. In contrast, linearity of tumor 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 VEGF-121. In highly proliferating tumors this rate appeared to be about 10 times higher than in low proliferating tumors. We conclude that the ratio between the VEGF-subtypes during tumor implantation and growth is a prerequisite for progression and hypothesize an individual and different response of each tumor cell line to VEGF.
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KEYWORD
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Angiogenesis factor, Carcinoma, squamous cell, Transplantation, heterologous
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