TY - JOUR
T1 - Insulin-like Growth Factor-II as a Paracrine Growth Factor in Human Neuroblastoma Cells
AU - Leventhal, Phillip S.
AU - Randolph, Ann E.
AU - Vesbit, Thomas E.
AU - Schenone, Angelo
AU - Windebank, Anthony J.
AU - Feldman, Eva L.
PY - 1995/11
Y1 - 1995/11
N2 - The human neuroblastoma line, SK-N-SH, has been subcloned into SH-SY5Y, a neuroblast N cell line, and SH-EP, an epithelial Schwann S cell line. We have previously shown that SH-SY5Y neuroblastoma cells produce insulin-like growth factor II (IGF-II), which acts by an autocrine mechanism to stimulate cell growth. In the current study, we examined the effect of IGF-II on SH-EP neuroblastoma cells. Northern blot and reverse transcriptase-polymerase chain reaction analyses indicate that SH-EP cells do not produce IGFI or IGF-II but express the type I and type II IGF receptors (IGF-IR and IGF-IIR). Cell surface expression of IGF-IR, assessed by fluorescence-activated sorting, was lower in SH-EP cells than in SH-SY5Y cells. Immunoprecipitation of IGF-IR, followed by anti-phosphotyrosine or anti-IGF-IR immunoblotting, demonstrated functional expression of these receptors in both cell types and confirmed the lower level of IGFIR expression in SH-EP cells. IGF-II promoted SH-EP cell growth in the presence of low concentrations of calf serum (0.1-0.3%) or 10 ng/ml epidermal growth factor (EGF). IGF-II stimulation of SH-EP growth was eliminated by the IGF-IR blocking antibody (αIR-3) but not by an IGF-IIR blocking antibody. Stimulation of cell growth via this receptor was also indicated by the ligand specificity for IGF analogs and insulin (IGFII ∼ IGF-I ∼ des(1-3)IGF-I ≫ insulin). These results indicate that in the presence of a permissive factor such as calf serum or EGF, IGF-II stimulates SH-EP cell growth via the IGF-IR. Collectively, these data suggest that within primary neuroblastomas, IGF-II may act as a paracrine factor to contribute to the promotion of S cell growth.
AB - The human neuroblastoma line, SK-N-SH, has been subcloned into SH-SY5Y, a neuroblast N cell line, and SH-EP, an epithelial Schwann S cell line. We have previously shown that SH-SY5Y neuroblastoma cells produce insulin-like growth factor II (IGF-II), which acts by an autocrine mechanism to stimulate cell growth. In the current study, we examined the effect of IGF-II on SH-EP neuroblastoma cells. Northern blot and reverse transcriptase-polymerase chain reaction analyses indicate that SH-EP cells do not produce IGFI or IGF-II but express the type I and type II IGF receptors (IGF-IR and IGF-IIR). Cell surface expression of IGF-IR, assessed by fluorescence-activated sorting, was lower in SH-EP cells than in SH-SY5Y cells. Immunoprecipitation of IGF-IR, followed by anti-phosphotyrosine or anti-IGF-IR immunoblotting, demonstrated functional expression of these receptors in both cell types and confirmed the lower level of IGFIR expression in SH-EP cells. IGF-II promoted SH-EP cell growth in the presence of low concentrations of calf serum (0.1-0.3%) or 10 ng/ml epidermal growth factor (EGF). IGF-II stimulation of SH-EP growth was eliminated by the IGF-IR blocking antibody (αIR-3) but not by an IGF-IIR blocking antibody. Stimulation of cell growth via this receptor was also indicated by the ligand specificity for IGF analogs and insulin (IGFII ∼ IGF-I ∼ des(1-3)IGF-I ≫ insulin). These results indicate that in the presence of a permissive factor such as calf serum or EGF, IGF-II stimulates SH-EP cell growth via the IGF-IR. Collectively, these data suggest that within primary neuroblastomas, IGF-II may act as a paracrine factor to contribute to the promotion of S cell growth.
UR - http://www.scopus.com/inward/record.url?scp=0028884767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028884767&partnerID=8YFLogxK
U2 - 10.1006/excr.1995.1365
DO - 10.1006/excr.1995.1365
M3 - Article
C2 - 7589243
AN - SCOPUS:0028884767
SN - 0014-4827
VL - 221
SP - 179
EP - 186
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -