두경부 편평상피세포암 세포주의 VEGF 아형의 분포와 종양증식 및 이종이식성 : relation to xenotransplantability and tumor progression in mice. = Quantitative analysis of VEGF-isoforms in head and neck squamous cell carcinoma cell lines

다국어 초록 (Multilingual Abstract)

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.