Cortistatin production by HepG2 human hepatocellular carcinoma cell line and distribution of somatostatin receptors.
OBJECTIVE
Recently, trials of octreotide have shown a significant survival benefit in the treatment of advanced hepatocellular carcinoma but new data are controversial. We, therefore, examined the production of somatostatin and cortistatin, the expression and distribution of somatostatin receptors (sst) in HepG2 human hepatocellular carcinoma cells, and the possible antiproliferative effect of octreotide on these cells.


METHODS
Radioimmunoassay and RT-PCR studies were performed for the detection of somatostatin and cortistatin. RT-PCR, radioligand binding and immunocytochemistry assays were employed for the detection of the ssts. Growth and viability of cells were measured by the tetrazolium salt assay.


RESULTS
HepG2 cells were found to express sst(2), sst(3) and sst(5) receptors. Immunocytochemistry revealed a mainly intracellular distribution of all ssts with unique patterns for each of them. Membrane binding sites for somatostatin were mainly of the sst(3) (39+/-8%) and sst(5) (59+/-5%) types, while only minor sst(2) binding could be detected (5+/-12%). Octreotide was found to inhibit the proliferation of HepG2 cells (IC(50) 1.25 x 10(-9)M) via protein tyrosine phosphatases. HepG2 cells produced cortistatin while somatostatin expression was not detected.


CONCLUSIONS
In conclusion, HepG2 cells express cortistatin, which regulates somatostatin receptors. Cell proliferation was reduced by octreotide via a protein tyrosine phosphatase dependent mechanism.
Notas
George
G
Laboratory of Gastroenterology and Hepatology, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
Kolios
George
G
Mastrodimou
Niki
N
Kampa
Marilena
M
Vasilaki
Anna
A
Xidakis
Costas
C
Castanas
Elias
E
Thermos
Kyriaki
K
Kouroumalis
Elias
E
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D015282:Octreotide / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics
D018931:Antineoplastic Agents, Hormonal; D009479:Neuropeptides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017481:Receptors, Somatostatin; C099323:cortistatin; D013004:Somatostatin; D004247:DNA; D015282:Octreotide