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 proliferative lesions, including malignant tumor growth and vascularization. As a result, cytotoxic agents that target cell surface FGF receptors are currently under investigation. Previous reports have shown that conjugation of basic FGF with the ribosome inactivator, saporin, results in a potent cytotoxin specific for cells bearing high-affinity FGF 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 receptors. The growth of three embryonal carcinoma cell lines and one embryonic stem cell line was shown to be inhibited by bFGF-saporin, suggesting 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 responses of CHO-KI cells, which also exhibit low numbers of high-affinity FGF receptors. Specifically, pretreatment with bFGF-saporin reduces the cloning efficiency of CHO-KI cells 8- to 10-fold, whereas bFGF-saporin has little or no effect on the cloning efficiency of embryonal carcinoma cells. This finding suggests that bFGF-saporin is cytotoxic for CHO-KI cells, but not for embryonal carcinoma cells. Thus, our findings argue strongly that other factors, in addition to high-affinity FGF receptor number, are important in determining sensitivity of cells to bFGF-saporin.
Miller
K
K
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.
Wilder
P J
PJ
Rizzino
A
A
D000818:Animals; D016466:CHO Cells; D018236:Carcinoma, Embryonal; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000922:Immunotoxins; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D000922:Immunotoxins; D010940:Plant Proteins; D017468:Receptors, Fibroblast Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D016222:Fibroblast Growth Factor 2; D009699:N-Glycosyl Hydrolases; D000076985:Saporins