Mol. Hum. Reprod. Advance Access originally published online on June 6, 2007
Molecular Human Reproduction 2007 13(8):567-576; doi:10.1093/molehr/gam039
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IGF-II regulates metastatic properties of choriocarcinoma cells through the activation of the insulin receptor
1 Hormone Laboratory, Department of Chemistry, Universidad Nacional de Colombia, Bogotá, Colombia 2 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden 3 Department of Clinical Sciences, Molecular Endocrinology Group, University of Las Palmas de G.C., Canary Institute for Cancer Research, RTICCC, Spain
4 Correspondence address. Tel: +57-1-316-5000 ext. 14466; Fax: +57-1-316-5220; E-mail: mysanchezd{at}unal.edu.co
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.
Key words: choriocarcinoma/hydatidiform mole/metastasis/IGF-II/insulin receptor
Submitted on March 12, 2007; resubmitted on April 19, 2007; accepted on April 23, 2007.
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