Insulin-like growth factor-I can mediate autocrine proliferation of human small lung cancer cell lines in vitro

Y. Nakanishi, J. L. Mulshine, P. G. Kasprzyk, R. B. Natale, R. Maneckjee, I. Avis, A. M. Treston, A. F. Gazdar, J. D. Minna, F. Cuttitta

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Abstract

The effect of insulin-like growth factor I (IGF-I) on growth of small cell lung cancer (SCLC) cell lines was studied. Western blot analysis of whole cell lysates of cell lines NCI-H345 and NCI-N417 demonstrated the presence of a 16-kD band consistent with an IGF-I precursor molecule. Scatchard plot analysis of cell line NCI-H345 using 125I-labeled IGF-I demonstrated two high affinity specific binding sites (K(d) 1.3 and 4.0 nM with maximal rate (B(max)) 200 and 500 fmol/mg protein, respectively). The exogenous addition of IGF-I, IGF-II, or insulin resulted in marked proliferation of human SCLC cells as evaluated using an in vitro growth assay. These peptides stimulate the growth of SCLC cell lines NCI-H82, NCI-H209, NCI-H345, and NCI-N417. The concentration of IGF-I producing maximal SCLC cell growth was 10-100-fold less than that of insulin or IGF-II, whereas the maximal growth stimulated by the optimal concentration of these peptides were similar. An MAb that specifically binds to the IGF-I receptor (but not to the insulin receptor) mediates a dose-dependent inhibition of cell growth in basal media as well as IGF-I, IGF-II, or insulin-supplemented media. The IGF-I receptor thus appears to be the common pathway for the mitogenic activity by IGF-I, IGF-II, and insulin for human SCLC cell lines. The demonstration of an IGF-I precursor molecule, specific IGF-I receptor binding, IGF-I-mediated growth stimulation, and inhibition of basal cell growth by an MAb to the IGF-I receptor suggests that an IGF-I-like molecule can function in vitro as an autocrine growth factor for human SCLC cell lines.

Original languageEnglish (US)
Pages (from-to)354-359
Number of pages6
JournalJournal of Clinical Investigation
Volume82
Issue number1
StatePublished - 1988

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Insulin-Like Growth Factor I
Lung Neoplasms
Small Cell Lung Carcinoma
Cell Line
IGF Type 1 Receptor
Insulin-Like Growth Factor II
Growth
Insulin
In Vitro Techniques
Peptides
Insulin Receptor
Intercellular Signaling Peptides and Proteins
Western Blotting
Binding Sites

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Nakanishi, Y., Mulshine, J. L., Kasprzyk, P. G., Natale, R. B., Maneckjee, R., Avis, I., ... Cuttitta, F. (1988). Insulin-like growth factor-I can mediate autocrine proliferation of human small lung cancer cell lines in vitro. Journal of Clinical Investigation, 82(1), 354-359.

Insulin-like growth factor-I can mediate autocrine proliferation of human small lung cancer cell lines in vitro. / Nakanishi, Y.; Mulshine, J. L.; Kasprzyk, P. G.; Natale, R. B.; Maneckjee, R.; Avis, I.; Treston, A. M.; Gazdar, A. F.; Minna, J. D.; Cuttitta, F.

In: Journal of Clinical Investigation, Vol. 82, No. 1, 1988, p. 354-359.

Research output: Contribution to journalArticle

Nakanishi, Y, Mulshine, JL, Kasprzyk, PG, Natale, RB, Maneckjee, R, Avis, I, Treston, AM, Gazdar, AF, Minna, JD & Cuttitta, F 1988, 'Insulin-like growth factor-I can mediate autocrine proliferation of human small lung cancer cell lines in vitro', Journal of Clinical Investigation, vol. 82, no. 1, pp. 354-359.
Nakanishi Y, Mulshine JL, Kasprzyk PG, Natale RB, Maneckjee R, Avis I et al. Insulin-like growth factor-I can mediate autocrine proliferation of human small lung cancer cell lines in vitro. Journal of Clinical Investigation. 1988;82(1):354-359.
Nakanishi, Y. ; Mulshine, J. L. ; Kasprzyk, P. G. ; Natale, R. B. ; Maneckjee, R. ; Avis, I. ; Treston, A. M. ; Gazdar, A. F. ; Minna, J. D. ; Cuttitta, F. / Insulin-like growth factor-I can mediate autocrine proliferation of human small lung cancer cell lines in vitro. In: Journal of Clinical Investigation. 1988 ; Vol. 82, No. 1. pp. 354-359.
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abstract = "The effect of insulin-like growth factor I (IGF-I) on growth of small cell lung cancer (SCLC) cell lines was studied. Western blot analysis of whole cell lysates of cell lines NCI-H345 and NCI-N417 demonstrated the presence of a 16-kD band consistent with an IGF-I precursor molecule. Scatchard plot analysis of cell line NCI-H345 using 125I-labeled IGF-I demonstrated two high affinity specific binding sites (K(d) 1.3 and 4.0 nM with maximal rate (B(max)) 200 and 500 fmol/mg protein, respectively). The exogenous addition of IGF-I, IGF-II, or insulin resulted in marked proliferation of human SCLC cells as evaluated using an in vitro growth assay. These peptides stimulate the growth of SCLC cell lines NCI-H82, NCI-H209, NCI-H345, and NCI-N417. The concentration of IGF-I producing maximal SCLC cell growth was 10-100-fold less than that of insulin or IGF-II, whereas the maximal growth stimulated by the optimal concentration of these peptides were similar. An MAb that specifically binds to the IGF-I receptor (but not to the insulin receptor) mediates a dose-dependent inhibition of cell growth in basal media as well as IGF-I, IGF-II, or insulin-supplemented media. The IGF-I receptor thus appears to be the common pathway for the mitogenic activity by IGF-I, IGF-II, and insulin for human SCLC cell lines. The demonstration of an IGF-I precursor molecule, specific IGF-I receptor binding, IGF-I-mediated growth stimulation, and inhibition of basal cell growth by an MAb to the IGF-I receptor suggests that an IGF-I-like molecule can function in vitro as an autocrine growth factor for human SCLC cell lines.",
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AU - Mulshine, J. L.

AU - Kasprzyk, P. G.

AU - Natale, R. B.

AU - Maneckjee, R.

AU - Avis, I.

AU - Treston, A. M.

AU - Gazdar, A. F.

AU - Minna, J. D.

AU - Cuttitta, F.

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N2 - The effect of insulin-like growth factor I (IGF-I) on growth of small cell lung cancer (SCLC) cell lines was studied. Western blot analysis of whole cell lysates of cell lines NCI-H345 and NCI-N417 demonstrated the presence of a 16-kD band consistent with an IGF-I precursor molecule. Scatchard plot analysis of cell line NCI-H345 using 125I-labeled IGF-I demonstrated two high affinity specific binding sites (K(d) 1.3 and 4.0 nM with maximal rate (B(max)) 200 and 500 fmol/mg protein, respectively). The exogenous addition of IGF-I, IGF-II, or insulin resulted in marked proliferation of human SCLC cells as evaluated using an in vitro growth assay. These peptides stimulate the growth of SCLC cell lines NCI-H82, NCI-H209, NCI-H345, and NCI-N417. The concentration of IGF-I producing maximal SCLC cell growth was 10-100-fold less than that of insulin or IGF-II, whereas the maximal growth stimulated by the optimal concentration of these peptides were similar. An MAb that specifically binds to the IGF-I receptor (but not to the insulin receptor) mediates a dose-dependent inhibition of cell growth in basal media as well as IGF-I, IGF-II, or insulin-supplemented media. The IGF-I receptor thus appears to be the common pathway for the mitogenic activity by IGF-I, IGF-II, and insulin for human SCLC cell lines. The demonstration of an IGF-I precursor molecule, specific IGF-I receptor binding, IGF-I-mediated growth stimulation, and inhibition of basal cell growth by an MAb to the IGF-I receptor suggests that an IGF-I-like molecule can function in vitro as an autocrine growth factor for human SCLC cell lines.

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