Effects of alpha-interferon on insulin-like growth factor-I, insulin-like growth factor-II and insulin-like growth factor binding protein-3 secretion by a human lung cancer cell line in vitro.
The aim of our study was to evaluate the effect of alpha-interferon (alpha-IFN) on cell growth and on the different IGF system components in a human non-small cell lung cancer line (Calu-6) in vitro. Our results confirm the release of IGF-I and IGF-II by these cells. The amount of IGF-II in conditioned media (10.25 +/- 3.95 nM/10(6) cells, mean +/- SE) was more than 10-fold higher than that of IGF-I. alpha-IFN treatment reduced IGF-II levels in the media, with a maximal effect between 1 and 10 U/ml (delta% of control: -31 and -55%, respectively, p < 0.05). IGF-I was significantly reduced at 0.5 U/ml (p < 0.01). No difference, however, was observed in IGF mRNA expression between untreated and alpha-IFN treated cells. An increase in IGF-I and IGF-II intracellular levels in alpha-IFN treated cultures was observed, suggesting that alpha-IFN can regulate the transfer of these peptides into the cells. Furthermore, IGF type-I and particularly type-lI receptor expression was increased after alpha-IFN treatment. IGFBP-3 was detected only in trace amounts in the conditioned media; however, it showed an increase after alpha-IFN treatment (+110% at 1 U/ml). IGFBP-3 mRNA expression showed a slight increase after treatment with 1 and 10 U/ml. alpha-IFN (1-10 U/ml) reduced the stimulatory effect of IGF-I on cell replication (p < 0.01), inhibited (p < 0.01) cell replication in untreated and in fetal calf serum (FCS)-stimulated cells, and increased apoptosis in Calu-6 cells. Our data suggest that alpha-IFN may exert its effects at the cellular level in part through modification of the local IGF system.
Del Monte
P
P
Division of Endocrinology, Galliera Hospital, Genova, Italy. patrizia.del.monte@galliera.it
Laurino
C
C
Arvigo
M
M
Palermo
C
C
Minuto
F
F
Barreca
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002455:Cell Division; D049109:Cell Proliferation; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis* / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000032:analysis* / Q000378:metabolism*; D016898:Interferon-alpha / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018972:Insulin-Like Growth Factor Binding Protein 3; D016898:Interferon-alpha; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II