Clinical & Experimental Metastasis

, Volume 15, Issue 6, pp 620–629

Effect of fibroblast growth factor saporin mitotoxins on human bladder cell lines

  • Tamara A. Tetzke
  • Maureen C. Caton
  • Pamela A. Maher
  • Zahra Parandoosh
Article

DOI: 10.1023/A:1018443430904

Cite this article as:
Tetzke, T.A., Caton, M.C., Maher, P.A. et al. Clin Exp Metastasis (1997) 15: 620. doi:10.1023/A:1018443430904

Abstract

Mitotoxins targeted via high-affinity growth factor receptors on the cell surface are a potential means of anticancer therapy. We have evaluated the effect of a chemically conjugated (FGF2-SAP) and a fusion protein (rFGF2-SAP) mitotoxin containing FGF-2 and saporin on normal (FHs 738B1) and malignant bladder cell lines (HT1197, TCCSUP, EJ-6, and RT4). The FGF-saporins demonstrated potent cytotoxicity in malignant bladder cell lines with an ID range of 0.13-13.6nM, whereas cells derived from normal fetal bladder (FHs 738B1) were less sensitive to FGF2-saporins (ID50>100nM). Greater than a 100-fold difference in cytotoxicity between FGF-saporins and unconjugated saporin was observed. Assessment of cellular FGF-2 content and secretion showed that FHs 738B1 and TCCSUP contained and secreted significantly more FGF-2 compared to other cell lines tested. 125I-FGF-2 receptor binding studies showed the presence of high-affinity (pM) FGF receptors on all bladder cell lines. Cross-linking studies revealed the presence of a major receptor-ligand complex of 90kDa on FHs 738B1 and 160-170kDa on the other bladder cell lines. All cell lines studied, except RT4, expressed solely FGFR-1. These studies demonstrate that FGF2-saporins have antiproliferative activity on human bladder cancer cell lines. However, the number of high-affinity FGF receptors, and FGF-2 cellular content and secretion are not absolute determinants of cellular sensitivity to FGF2-saporins.

bladder FGF receptor fibroblast growth factor (FGF-2), mitotoxin saporin 

Copyright information

© Chapman and Hall 1997

Authors and Affiliations

  • Tamara A. Tetzke
    • 1
  • Maureen C. Caton
    • 1
  • Pamela A. Maher
    • 2
  • Zahra Parandoosh
    • 1
  1. 1.Prizm Pharmaceuticals IncSan DiegoUSA
  2. 2.Department of Cell BiologyThe Scripps Research InstituteLa JollaUSA