IGF-II regulates metastatic properties of choriocarcinoma cells through the activation of the insulin receptor.
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.
Diaz
L E
LE
Hormone Laboratory, Department of Chemistry, Universidad Nacional de Colombia, Bogotá, Colombia.
Chuan
Y-C
YC
Lewitt
M
M
Fernandez-Perez
L
L
Carrasco-Rodríguez
S
S
Sanchez-Gomez
M
M
Flores-Morales
A
A
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D002822:Choriocarcinoma / Q000378:metabolism / Q000556:secondary*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000819:agonists / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology*
D015703:Antigens, CD; D009281:Naphthalenes; D063065:Organophosphonates; C519736:hydroxy-2-naphthalenyl-methyl phosphonic acid trisacetoxymethylester; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C435941:INSR protein, human; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases