EFFECT OF FIBROBLAST GROWTH-FACTOR SAPORIN MITOTOXINS ON HUMAN BLADDER CELL-LINES

Mitotoxins targeted via high-affinity growth factor receptors on the c ell surface are a potential means of anticancer therapy. We have evalu ated the effect of a chemically conjugated (FGF2-SAP) and a fusion pro tein (rFGF2-SAP) mitotoxin containing FGF-2 and saporin on normal (FHs 738B1) and malignant bladder cell lines (HT1197, TCCSUP, EJ-6, and RT 4). The FGF-saporins demonstrated potent cytotoxicity in malignant bla dder cell lines with an ID50 range of 0.13-13.6 nM, whereas cells deri ved from normal fetal bladder (FHs 738B1) were less sensitive to FGF2- saporins (ID50>100 nM). Greater than a 100-fold difference in cytotoxi city between FGF-saporins and unconjugated saporin was observed. Asses sment of cellular FGF-2 content and secretion showed that FHs 738B1 an d TCCSUP contained and secreted significantly more FGF-2 compared to o ther cell lines tested. I-125-FGF-2 receptor binding studies showed th e presence of high-affinity (pM) FGF receptors on all bladder cell lin es. Cross-linking studies revealed the presence of a major receptor-li gand complex of 90 kDa on FHs 738B1 and 160-170 kDa on the other bladd er cell lines. All cell lines studied, except RT4, expressed solely FG FR-1. These studies demonstrate that FGF2-saporins have antiproliferat ive activity on human bladder cancer cell lines. However, the number o f high-affinity FGF receptors, and FGF-2 cellular content and secretio n are not absolute determinants of cellular sensitivity to FGF2-sapori ns.