Konerding M A, Fait E, Dimitropoulou C, Malkusch W, Ferri C, Giavazzi R, Coltrini D, Presta M
Department of Anatomy, Johannes Gutenberg-Universität Mainz, Germany.
Am J Pathol. 1998 Jun;152(6):1607-16.
Three cell clones originated by transfection of human endometrial adenocarcinoma HEC-1-B cells with fibroblast growth factor-2 (FGF-2) cDNA and characterized by a different capacity to produce and secrete the growth factor were transplanted subcutaneously in nude mice. Corrosion casting of the tumor microvasculature of xenografts produced by injection of 2 x 10(6) or 10 x 10(6) FGF-2-B9 cells (which produce and secrete significant amounts of FGF-2), 10 x 10(6) FGF-2-A8 cells (which produce comparable amounts of FGF-2 but do not secrete it), or 10 x 10(6) control FGF-2-B8 cells (which produce only trace amounts of FGF-2) was performed after 14 days of growth. Interbranching distances, intervascular distances, branching angles, and vessel diameters were then determined using tridimensional stereo pairs of the casted tumor vascularity. When transplanted at the same concentration, FGF-2-B9 cells grew faster in nude mice compared with FGF-2-A8 and FGF-2-B8 clones. The total amount of new vessel formation was far higher in FGF-2-B9 tumors than in FGF-2-B8 or FGF-2-A8 tumors. Also, vessel courses were more irregular and blind-ending vessels and evasates were more frequent in FGF-2-B9 tumors. Moreover, FGF-2-B9 tumor microvasculature was characterized by a wider average vascular diameter and by an extreme variability of the diameter of each individual vessel along its course between two ramifications. No statistical differences were observed when the distribution curves of the values of intervascular distances, interbranching distances, and branching angles of the microvessel network were compared among the different experimental groups. The distinctive features of the microvasculature of FGF-2-B9 tumors were retained, at least in part, in the smaller lesions produced by injection of a limited number of cells. The data indicate that FGF-2 production and release confer to FGF-2-B9 cells the ability to stimulate the formation of new blood vessels with distinctive architectural features. Neovascularization of FGF-2-B9 lesions parallels the faster rate of growth of the neoplastic parenchyma. This does not affect the overall architecture of the microvessel network that appears to be primed by characteristics of the HEC-1-B tumor cell line and/or by the microenvironment of the host. To our knowledge, this work represents the first attempt to define the influence of a single, defined growth factor on the tridimensional tumor vascular pattern.
将人子宫内膜腺癌HEC - 1 - B细胞用成纤维细胞生长因子2（FGF - 2）cDNA转染后产生的三个细胞克隆，因其产生和分泌生长因子的能力不同而被鉴定，将它们皮下移植到裸鼠体内。在分别注射2×10⁶或10×10⁶个FGF - 2 - B9细胞（产生并分泌大量FGF - 2）、10×10⁶个FGF - 2 - A8细胞（产生等量FGF - 2但不分泌）或10×10⁶个对照FGF - 2 - B8细胞（仅产生微量FGF - 2）后14天，对异种移植瘤的肿瘤微血管进行腐蚀铸型。然后使用铸型肿瘤血管的三维立体对来确定分支间距离、血管间距离、分支角度和血管直径。当以相同浓度移植时，与FGF - 2 - A8和FGF - 2 - B8克隆相比，FGF - 2 - B9细胞在裸鼠体内生长更快。FGF - 2 - B9肿瘤中新生血管形成的总量远高于FGF - 2 - B8或FGF - 2 - A8肿瘤。此外，FGF - 2 - B9肿瘤中的血管走向更不规则，盲端血管和渗出物更常见。而且，FGF - 2 - B9肿瘤微血管的特征是平均血管直径更宽，且每个单独血管在两个分支之间的行程中直径变化极大。在比较不同实验组微血管网络的血管间距离、分支间距离和分支角度值的分布曲线时，未观察到统计学差异。FGF - 2 - B9肿瘤微血管的独特特征至少部分保留在注射有限数量细胞产生的较小病变中。数据表明，FGF - 2的产生和释放赋予FGF - 2 - B9细胞刺激形成具有独特结构特征的新血管的能力。FGF - 2 - B9病变的新生血管形成与肿瘤实质更快的生长速度平行。这并不影响微血管网络的整体结构，微血管网络似乎由HEC - 1 - B肿瘤细胞系的特征和/或宿主的微环境所决定。据我们所知，这项工作代表了首次尝试确定单一、明确的生长因子对三维肿瘤血管模式的影响。
