FERNANDEZ Maria Celia
Insulin-like Growth Factor-1 (IGF-1) Regulates Pheochromocytoma Cell Proliferation and Survival In vitro and In vivo.
FERNANDEZ MARIA CELIA; VENARA MARCELA; NOWICKI SUSANA; CHEMES HECTOR; BARONTINI MARTA; PENNISI PATRICIA
Año: 2012 vol. 153 p. 3724 - 3734
Insulin-like Growth Factors are involved in malignant transformation and growth of several tissues, including the adrenal medulla. The present study was designed to evaluate the impact of IGF-1 on pheochromocytoma development. We used a murine pheochromocytoma cell line (MPC4/30) and an animal model with a reduction of 75% in circulating IGF-1 levels (Liver- IGF-1- Deficient mice, LID) to perform studies in vitro and in vivo. We found that, in culture, IGF-1 stimulation increases proliferation, migration and anchorage-independent growth, while inhibits apoptosis of MPC cells. When injected to control and to LID mice MPC cells grow and form tumors with features of pheochromocytoma. Six weeks after cell inoculation, all control mice developed subcutaneous tumors. In contrast, in 73% of LID mice tumor development was delayed to 7-12 weeks and the remaining 27% did not develop tumors up to 12 weeks after inoculation. LID mice harboring MPC cells and treated with rhIGF-1 (LID+), developed tumors as controls. Tumors developed in Control, LID and LID+ mice had similar histology and were similarly positive for IGF-1R expression. The apoptotic index was higher in tumors from LID mice compared to those from control mice, while vascular density was decreased. In summary, our work demonstrates that IGF-1 has a critical role in maintaining tumor phenotype and survival of already transformed pheochromocytoma cells and is required for the initial establishment of these tumors, providing encouragement to carry on research studies to address the IGF-1/IGF-1R system as a target of therapeutic strategies for pheochromocytoma treatment in the future.