These findings suggest a possible role of IGF-IEc in NEN tumorigenesis and progression to metastases that could be used as an additional new marker of a more aggressive behavior and a potential drugable target.
Our study also demonstrated that PADI4 contributes to tumor metastasis by regulating the gene expression of insulin-like growth factor 1 (IGF1) and WAS/WASL-interacting protein family member 1 (WIPF1).
IGF-IR expression was a predictor of metastases in pediatric adrenocortical tumors in univariate analysis (hazard ratio 1.84; 95% confidence interval 1.28-2.66; P = 0.01).
Immunoreactivity of IGF-I and cognate receptor positively correlated with tumor diameter and wide intrathyroidal extension but not with patient's gender and age or with the stage of the tumors and the occurrence of limph node metastases.
Increased expression of insulin-like growth factor I and/or its receptor in gastrinomas is associated with low curability, increased growth, and development of metastases.
When the IGF-1R was reexpressed in the M12 subline using a retroviral expression vector, M12-LISN, to a receptor number similar to that of the P69SV40-T parental cell line, the authors demonstrated a marked decrease in colony formation in soft agar in the M12-LISN cells vs the M12 control cells (p < or = 0.01), and a decrease in vivo tumor growth and metastases when injected either subcutaneously or an intraprostatic location (p < or = 0.01).