Fibroblast growth factor complexed to the cytotoxin saporin is growth inhibitory but not cytotoxic for embryonal carcinoma cells

Keith Miller, Phillip J. Wilder, Angie Rizzino

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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 of bFGF-saporin.

Original languageEnglish (US)
Pages (from-to)69-78
Number of pages10
JournalCytotechnology
Volume13
Issue number2
DOIs
StatePublished - Jan 1993

Keywords

  • FGF receptors
  • cytotoxin
  • embryonal carcinoma cells
  • fibroblast growth factor
  • saporin

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Clinical Biochemistry
  • Cell Biology

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