Insulin-like growth factor-I can mediate autocrine proliferation of human small cell lung cancer cell lines in vitro.
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 (Kd 1.3 and 4.0 nM with maximal rate (Bmax) 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 stimulated 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.
Nakanishi
Y
Y
Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland 20814.
Mulshine
J L
JL
Kasprzyk
P G
PG
Natale
R B
RB
Maneckjee
R
R
Avis
I
I
Treston
A M
AM
Gazdar
A F
AF
Minna
J D
JD
Cuttitta
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000302:isolation & purification / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D011498:Protein Precursors / Q000302:isolation & purification; D011972:Receptor, Insulin / Q000032:analysis / Q000276:immunology; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D006131:Growth Inhibitors; D007328:Insulin; D011498:Protein Precursors; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin