|Title:||IGF-II regulates metastatic properties of choriocarcinoma cells through the activation of the insulin receptor||Authors:||Diaz, L. E.
Chuan, Y. C.
|Issue Date:||2007||Publisher:||1360-9947||Project:||Mecanismos Moleculares y Celulares de Señalización Intracelular en Respuesta A la Hormona de Crecimiento Humana: la Vía Jak (Janus Kinase) Stat (Signal Transducer And Activator Of Transcription) Co||Journal:||Molecular Human Reproduction||Abstract:||Choriocarcinoma is a highly malignant tumor that can arise from trophoblasts of any type of gestational event but most often from complete hydatidiform mole. IGF-II plays a fundamental role in placental development and may play a role in gestational trophoblastic diseases. Several studies have shown that IGF-II is expressed at high levels in hydatidiform moles and choriocarcinoma tissues; however, conflicting data exist on how IGF-II regulates the behaviour of choriocarcinoma cells. The purpose of this study was to determine the contribution of the receptors for IGF-I and insulin to the actions of IGF-II on the regulation of choriocarcinoma cells metastasis. An Immuno Radio Metric Assay was used to analyse the circulating and tissue levels of IGF-I and IGF-II in 24 cases of hydatidiform mole, two cases of choriocarcinoma and eight cases of spontaneous abortion at the same gestational age. The JEG-3 choriocarcinoma cell line was used to investigate the role of IGF-II in the regulation of cell invasion. We found that mole and choriocarcinoma tissue express high levels of IGF-II compared to first trimester placenta. Both IGF-I and IGF-II regulate choriocarcinoma cell invasion in a dose dependent manner but through a different mechanism. IGF-II effects involve the activation of the InsR while IGF-I uses the IGF-IR. The positive effects of IGF-II on invasion are the result of enhanced cell adhesion and chemotaxis (specifically towards collagen IV). The actions of IGF-II but not those of IGF-I were sensitive to inhibition by the insulin receptor inhibitor HNMPA(AM)3. Our results demonstrate that the insulin receptor regulates choriocarcinoma cell invasion. © The Author 2007.||URI:||http://hdl.handle.net/10553/48254||ISSN:||1360-9947||DOI:||10.1093/molehr/gam039||Source:||Molecular Human Reproduction[ISSN 1360-9947],v. 13, p. 567-576|
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