Fibroblast deficiency of Insulin-Like Growth Factor 1 Receptor Type 1 (IGF1R) impairs initial steps of murine pheochromocytoma development

MARTÍN, AYELEN; VENARA MARCELA; MATHO, CECILIA; OLEA DANIELA FERNANDA; FERNANDEZ, MARÍA CELIA; PENNISI PATRICIA A

BIOCHIMIE

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Lugar: Paris; Año: 2019 p. 108 - 116

0300-9084

Insulin-like growth factor 1 (IGF1) has a critical role in maintainingtumor phenotype and survival of already transformed murinepheochromocytoma (pheo) cells (MPC4/30) and it is required for theinitial establishment of these tumors. However, the role of localIGF1/IGF1R system in tumor microenvironment has not been fullyunderstood. In vivo, by subcutaneous injection of pheo cells inheterozygous IGF1R knockout mice (L/n), we found that the time ofnoticeable tumor appearance was delayed, and incidence was decreased inL/n group compared to control (L/L) mice. Once established, tumorproliferation, vascularization or growth rate did not differ betweengroups. In vitro, fibroblast from L/n and L/L mice were cultured togenerate conditioned media (CM) and differential matrixes on which pheocells were seeded. Proliferation rate was higher when pheo cells werecultured with CM, or in differential matrix generated by L/L murinefibroblasts. A diminished fibronectin (FN) expression and secretion fromL/n fibroblast was associated with decreased expression of integrinsubunits in tumor cells. Also, soluble factors as IGF1 and insulin-likegrowth factor binding protein 2 (IGFBP2) were reduced. Our data suggestthat IGF1 signaling through IGF1R may contribute to tumor cells anchorageand survival by interaction with both matrix and soluble factors producedby tumor microenvironment fibroblasts.