Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth

Abstract

Unlike normal melanocytes, primary and metastatic human melanomas express high levels of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) messenger RNA, and expression of these genes is essential in sustaining the proliferation of malignant melanomas in vitro. To determine whether bFGF and FGFR-1 are also required for tumor formation in these cells, liposome-mediated gene transfer was used to deliver episomal vectors containing antisense-oriented bFGF or FGFR-1 cDNAs into human melanomas, grown as subcutaneous tumors in nude mice. The growth of tumors injected with these constructs was completely arrested or the tumors regressed as a result of blocked intratumoral angiogenesis and subsequent necrosis. Thus, inhibition of bFGF/FGFR-1-mediated signaling may open a new avenue for the treatment of advanced-stage melanomas.