Autocrine growth stimulation by secreted Kaposi fibroblast growth factor but not by endogenous basic fibroblast growth factor.
We studied the different potentials of a secreted and a nonsecreted member of the fibroblast growth factor (FGF) family to induce autocrine growth stimulation in human adrenal cortex carcinoma cells (SW-13). These epithelial cells express basic FGF (bFGF) cell surface receptors, and picomolar concentrations of bFGF suffice to induce anchorage-independent growth. The requirement for exogenously added bFGF contrasts with the intracellular storage of biologically active bFGF in SW-13 cells greater than 10,000-fold in excess of the concentration needed to stimulate anchorage independent growth. To study whether the expression of a secreted FGF would alter the growth phenotype of these cells, we transfected them with an expression vector coding for the Kaposi-fgf (K-fgf) oncogene. In contrast to controls, K-fgf-transfected cells secrete significant amounts of biologically active K-fgf protein into the growth media, show up to 50-fold increased colony formation in soft agar, and grow into rapidly progressing, highly vascularized tumors in athymic nude mice. A reversible inhibition of the autocrine growth stimulation in vitro is brought about by the polyanionic compound suramin. We conclude that FGF has to be released from SW-13 cells to function fully as a growth stimulator in vitro and in vivo.
Wellstein
A
A
Medicine Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892.
Lupu
R
R
Zugmaier
G
G
Flamm
S L
SL
Cheville
A L
AL
Delli Bovi
P
P
Basilico
C
C
Lippman
M E
ME
Kern
F G
FG
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015536:Down-Regulation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors; D006493:Heparin / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014410:Tumor Stem Cell Assay
C496445:FGF4 protein, human; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D013498:Suramin; D005346:Fibroblast Growth Factors; D006493:Heparin