ABSTRACT
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 s.c. in nude mice. Corrosion casting of the tumor microvasculature of xenografts produced by injection of 2x106 or 10x106 FGF-2-B9 cells (that produce and secrete significant amounts of FGF-2), 10x106 FGF-2-A8 cells (that produce comparable amounts of FGF-2 but do not secrete it), or 10x106 control FGF-2-B8 cells (that 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 3D stereo pairs of the casted tumor vascularity.
When transplanted at the same concentration, FGF-2-B9 cells grew faster in nude mice compared to 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 instead 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 morphological 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 3D tumor vascular pattern.
Am. J. Pathol. (1998) 152:1607-1616