FIBROBLAST GROWTH-FACTOR COMPLEXED TO THE CYTOTOXIN SAPORIN IS GROWTH-INHIBITORY BUT NOT CYTOTOXIC FOR EMBRYONAL CARCINOMA-CELLS

Fibroblast growth factors (FGFs) have been implicated in a number of p roliferative lesions, including malignant tumor growth and vasculariza tion. As a result, cytotoxic agents that target cell surface FGF recep tors are currently under investigation. Previous reports have shown th at conjugation of basic FGF with the ribosome inactivator, saporin, re sults in a potent cytotoxin specific for cells bearing high-affinity F GF receptors. In this report, we have used this FGF receptor-dependent cytotoxin to study receptor interactions at the surface of embryonal carcinoma cells, which express low numbers of high-affinity FGF recept ors. The growth of three embryonal carcinoma cell lines and one embryo nic stem cell line was shown to be inhibited by bFGF-saporin, suggesti ng that these cells are able to bind and internalize FGF through high- affinity FGF receptors. In addition, we determined that the responses of these cells to bFGF-saporin are qualitatively different than the re sponses of CHO-KI cells, which also exhibit low numbers of high-affini ty FGF receptors. Specifically, pretreatment with bFGF-saporin reduces the cloning efficiency of CHO-KI cells 8- to 10-fold, whereas bFGF-sa porin has little or no effect on the cloning efficiency of embryonal c arcinoma cells. This finding suggests that bFGF-saporin is cytotoxic f or CHO-KI cells, but not for embryonal carcinoma cells. Thus, our find ings argue strongly that other factors, in addition to high-affinity F GF receptor number, are important in determining sensitivity of cells to bFGF-saporin.