Insulin-like Growth Factor-II as a Paracrine Growth Factor in Human Neuroblastoma Cells

Phillip S. Leventhal, Ann E. Randolph, Thomas E. Vesbit, Angelo Schenone, Anthony John Windebank, Eva L. Feldman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)179-186
Number of pages8
JournalExperimental Cell Research
Volume221
Issue number1
DOIs
StatePublished - Nov 1995

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Insulin-Like Growth Factor II
Neuroblastoma
Intercellular Signaling Peptides and Proteins
Growth
Blocking Antibodies
Epidermal Growth Factor
Insulin
IGF Type 2 Receptor
Cell Line
IGF Type 1 Receptor
Phosphotyrosine
Schwann Cells
Reverse Transcriptase Polymerase Chain Reaction
Serum
Insulin-Like Growth Factor I
Immunoprecipitation
Immunoblotting
Northern Blotting

ASJC Scopus subject areas

  • Cell Biology

Cite this

Insulin-like Growth Factor-II as a Paracrine Growth Factor in Human Neuroblastoma Cells. / Leventhal, Phillip S.; Randolph, Ann E.; Vesbit, Thomas E.; Schenone, Angelo; Windebank, Anthony John; Feldman, Eva L.

In: Experimental Cell Research, Vol. 221, No. 1, 11.1995, p. 179-186.

Research output: Contribution to journalArticle

Leventhal, Phillip S. ; Randolph, Ann E. ; Vesbit, Thomas E. ; Schenone, Angelo ; Windebank, Anthony John ; Feldman, Eva L. / Insulin-like Growth Factor-II as a Paracrine Growth Factor in Human Neuroblastoma Cells. In: Experimental Cell Research. 1995 ; Vol. 221, No. 1. pp. 179-186.
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abstract = "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.",
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