IMPACT OF FIBROBLAST GROWTH FACTOR-2 ON TUMOR MICROVASCULAR ARCHITECTURE - A TRIDIMENSIONAL MORPHOMETRIC STUDY

Three cell clones originated by transfection of human endometrial aden ocarcinoma HEC-1-B cells with fibroblast growth factor-2 (FGF-2) cDNA and characterized by a different capacity to produce and secrete the g rowth factor were transplanted subcutaneously in nude mice. Corrosion casting of the tumor microvasculature of xenografts produced by inject ion of 2 x 10(6) or 10 x 10(6) FGF-2-B9 cells (which produce and secre te significant amounts of FGF-2), 10 x 10(6) FGF-2-A8 cells (which pro duce 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) wa s performed after 14 days of growth, Inter-branching distances, interv ascular distances, branching angles, and vessel diameters were then de termined using tridimensional stereo pairs of the casted tumor vascula rity. 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 t otal 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 ir regular and blind-ending vessels and evasates were more frequent in FG F-2-B9 tumors. Moreover, FGF-2-B9 tumor microvasculature was character ized by a wider average vascular diameter and by an extreme variabilit y of the diameter of each individual vessel along its course between t wo ramifications, No statistical differences were observed when the di stribution curves of the values of intervascular distances, interbranc hing distances, and branching angles of the microvessel network were c ompared among the different experimental groups. The distinctive featu res of the microvasculature of FGF-2-B9 tumors were retained, at least in part, in the smaller lesions produced by injection of a limited nu mber of cells. The data indicate that FGF-2 production and release con fer to FGF-2-B9 cells the ability to stimulate the formation of new bl ood vessels with distinctive architectural features. Neovascularizatio n of FGF-2-B9 lesions parallels the faster rate of growth of the neopl astic parenchyma, This does not affect the overall architecture of the microvessel network that appears to be primed by characteristics of t he 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 th e influence of a single, defined growth factor on the tridimensional t umor vascular pattern.