RGD Reference Report - IGF-II regulates metastatic properties of choriocarcinoma cells through the activation of the insulin receptor. - Rat Genome Database

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IGF-II regulates metastatic properties of choriocarcinoma cells through the activation of the insulin receptor.

Authors: Diaz, LE  Chuan, YC  Lewitt, M  Fernandez-Perez, L  Carrasco-Rodriguez, S  Sanchez-Gomez, M  Flores-Morales, A 
Citation: Diaz LE, etal., Mol Hum Reprod. 2007 Aug;13(8):567-76. Epub 2007 Jun 6.
RGD ID: 2290454
Pubmed: (View Article at PubMed) PMID:17556377
DOI: Full-text: DOI:10.1093/molehr/gam039

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.


Disease Annotations    
choriocarcinoma  (IDA,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Igf2  (insulin-like growth factor 2)
Insr  (insulin receptor)

Genes (Mus musculus)
Igf2  (insulin-like growth factor 2)
Insr  (insulin receptor)

Genes (Homo sapiens)
IGF2  (insulin like growth factor 2)
INSR  (insulin receptor)

Additional Information