Endocrine Abstracts (2009) 20 P540

IGFBP3 and IGFBP2 negatively and positively modulate IGFs autocrine effect in lung cancer cell lines

Marica Arvigo, Federico Gatto, Pietro Ameri, Diego Ferone & Francesco Minuto


Department of Endocrinology and Medical Sciences and Centre of Excellence for Biomedical Research, University of Genova, Genova, Italy.


Insulin-like growth factors (IGFs) play an important role in the pathogenesis of several neoplasias and the IGF-binding proteins (IGFBPs) may have a role as autocrine/paracrine factors in regulating the local actions of the IGFs. In the present study we investigated IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3 production in cultured media from three human lung cancer cell lines (Calu-3, Calu-6, A549) and in human neoplastic and normal lung tissue samples obtained at surgery from 8 patients. Calu-6 cells secreted much more IGF-II than Calu-3 and A549 (190, 25, and 5 ng/107 cells respectively) and much less IGF-I (0.7, 13, and 5 ng/107 cells). Conversely, IGFBP-1 and IGFBP-3 were most abundant in media conditioned by CALU-3 (13 and 120 ng/107 cells respectively) and least abundant in CALU-6 (<1 ng/107 cells). Molar ratio between IGF-I+IGF-II and IGFBP-1+IGFBP-3 was much higher in Calu-6 which is also the most actively replicating cell line. Regarding IGFBP-2 we found a higher concentration in Calu-6 than in Calu-3 and A549 conditioned media. In consideration of the enhancing action of IGFBP-2 on IGF bioactivity this finding further supports the high replication rate of Calu-6 cell line. Regarding tissue we found a significantly higher concentration of IGF-I in neoplastic (18±3.6 ng/g of tissue) than in normal (7.8±1.5 ng/g of tissue) lung tissue in all subject studied. IGF-II concentration was higher than IGF-I, but the difference between neoplastic and normal tissue was not significant (90.3±15.5 and 61.1±11.8 ng/g of tissue respectively). Neither the normal nor the neoplastic lung tissue produced significant amounts of IGFBP-1. IGFBP-2 and IGFBP-3, as evaluated by immunoassays and immunoblot were predominantly expressed in neoplastic tissue as compared to normal. These data raise the possibility that IGFBPs are important modulators of lung cancer proliferation by inhibiting (IGFBP-3) or stimulating (IGFBP-2) the autocrine mitogenic effects of IGFs.

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