Local deficiency of Insulin-like Growth Factor-I Receptor (IGF-IR) modulates the initial steps of experimental Pheochromocytoma (Pheo) development.

MARTIN, AYELÉN; FERNÁNDEZ, MARÍA CELIA; MATHÓ, CECILIA; VENARA, MARCELA; PENNISI, PATRICIA

Milan

Congreso; 9th Joint Meeting of Pediatric Endocrinology, ESPE, PES, APEG, APPES, ASPAE, JSPE, SLEP.; 2013

We have previously shown that circulating IGF-I has a critical role in maintaining tumor phenotype and survival of already transformed pheochromocytoma cells (MPC4/30), and is required for the initial establishment of these tumors. However, the role of the local IGF-I/IGF-IR system that is present in the tumor microenvironment -which includes endothelial cells, fibroblasts and extracellular matrix- has not been fully understood. Herein, we used a murine model of pheochromocytoma by subcutaneous injection of 1x106 MPC4/30 cells in heterozygous IGF-IR knockout mice (IGF-IR+/n) and we found that the time of noticeable tumor appearance was delayed in IGF-IR+/n group (n=53) compared to control IGF-IR+/+ mice (C, n=79) [6 vs 5 weeks, Hazard Ratio: 0.27; 95% CI: 0.16- 0.46]. Additionally, 9.43% of IGF-IR+/n mice did not develop tumor (p