NEOVASCULARIZATION IS ASSOCIATED WITH A SWITCH TO THE EXPORT OF BFGF IN THE MULTISTEP DEVELOPMENT OF FIBROSARCOMA

In a transgenic mouse model, dermal fibrosarcomas develop in a pathway comprised of at least three stages: mild fibromatosis, aggressive fibromatosis, and fibrosarcoma. The latter two stages are highly vascularized when compared with both the normal dermis and the initial mild lesion. Analysis of cell cultures derived from biopsies of these lesions has revealed that basic fibroblast growth factor (bFGF) is synthesized in all three stages and in normal dermal fibroblasts derived from the same mice. Unexpectedly, there is a change in the localization of bFGF from its normal cell-associated state to extracellular release in the latter two stages, which is concomitant both with the neovascularization seen in vivo and with the tumorigenicity of these cell lines. Thus, in this multistep tumorigenesis pathway there appears to be a discrete switch to the angiogenic phenotype that correlates with the export of bFGF, a known angiogenic factor.