Sodium iodide symporter is expressed at the preneoplastic stages of liver carcinogenesis and in human cholangiocarcinoma.
OBJECTIVE
The ability of thyroid cells to take up iodide, which enables (131)I radiotherapy for thyroid cancer, is due to the expression of the sodium iodide symporter at their plasma membrane. Expression of this symporter has been found in some nonthyroid cancers. However, it is mostly accumulated in the cytoplasm, and its functionality has not been demonstrated. We have investigated sodium iodide symporter expression and functionality in human liver cancer, and in a diethylnitrosamine induced Wistar rat model of primary liver cancer at different stages of carcinogenesis.


METHODS
Sodium iodide symporter mRNA and protein were studied in tissues from patients with hepatocellular- or cholangio-carcinomas using reverse-transcription polymerase chain reaction, immunoblot, and immunohistochemistry. We studied the dynamics of hepatic iodine uptake in the animal model using nuclear imaging.


RESULTS
Sodium iodide symporter expression showed up in all 20 cholangiocarcinomas, but in only 2 of the 26 hepatocellular carcinomas, investigated. It was also found in normal bile duct cells and in the ductular reaction present in cirrhotic tissues. It was located at the plasma membrane in 10 of 20 cholangiocarcinoma. In rat liver cancer, a functional sodium iodide symporter expression was triggered as from the early preneoplastic steps, and was amplified during clonal tumor cell expansion, allowing complete tumor suppression after (131)I radiotherapy.


CONCLUSIONS
A significant proportion of human cholangiocarcinomas expresses membrane sodium iodide symporter, which may permit radioiodine therapy. Our data also suggest that (131)I acts on a crucial target for liver cancer development.
Liu
Bingkai
B
INSERM, U785, Centre Hépatobiliaire, Villejuif, France; Université Paris-Sud, Faculté de médecine, Villejuif, France.
Hervé
Julie
J
Bioulac-Sage
Paulette
P
Valogne
Yannick
Y
Roux
Jérôme
J
Yilmaz
Funda
F
Boisgard
Raphaël
R
Guettier
Catherine
C
Calès
Paul
P
Tavitian
Bertrand
B
Samuel
Didier
D
Clerc
Jérôme
J
Bréchot
Christian
C
Faivre
Jamila
J
D000818:Animals; D001345:Autoradiography; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007455:Iodine; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D000099209:Sodium-Iodide Symporters
D007455:Iodine; D012333:RNA, Messenger; D027981:Symporters; D000099209:Sodium-Iodide Symporters