Autocrine regulation of growth by insulin-like growth factor (IGF)-II mediated by type I IGF-receptor in Wilms tumor cells.
Wilms tumor is a common embryonic tumor in childhood. Two Wilms tumor-suppressor genes, WT1 and WT2, are located on chromosome 11p, WT2 at 11p15.5 close to the IGF-II gene, which is highly expressed in some Wilms tumors. We established Wilms tumor cell lines to investigate the regulation of tumor cell growth by IGF-II. We demonstrated that Wilms tumor cells produce more IGF-II than normal kidney cells. Both types I and II IGF receptors reside on these cells. In serum-free culture medium, tumor cell growth is reversibly inhibited by suramin via interfering with IGF-II binding. Wilms tumor cell growth is also arrested by IGF binding protein-3, capturing the continuously produced IGF-II, and by alpha IR-3, a type I IGF receptor-blocking antibody. Thus, we demonstrated the whole loop of elevated synthesis, secretion, receptor binding, and autocrine growth stimulation of IGF-II through type I IGF receptor in Wilms tumor cell cultures. We concluded that IGF-II plays a crucial role in the regulation of growth of this embryonic tumor. Overproduction of IGF-II by the tumor cell is the limiting step for Wilms tumor growth, supporting its important role as an embryonic growth factor.
Qing
R Q
RQ
Department of Pediatrics, University of Zurich, Switzerland.
Schmitt
S
S
Ruelicke
T
T
Stallmach
T
T
Schoenle
E J
EJ
D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D009396:Wilms Tumor / Q000473:pathology*
D013498:Suramin; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1