Human cholangiocarcinomas express somatostatin receptors and respond to somatostatin with growth inhibition.
BACKGROUND/AIMS: Cholangiocarcinoma, a malignancy of biliary epithelia, is usually fatal because of absence of tests for early detection and lack of effective therapy. Somatostatin ( SS) receptors are expressed in several malignancies and in rodent biliary epithelia. We tested the hypothesis that SS receptors are present in cholangiocarcinomas. METHODS: We examined tissue from seven surgically resected human cholangiocarcinomas and a human bile duct cancer cell line for the messenger RNA for one subtype of SS receptors ( SSTR2) and studied binding and growth-active properties of SS and its analogues. RESULTS: SSTR2 messenger RNA was expressed in all seven human cholangiocarcinoma specimens. Experiments with the human cholangiocarcinoma cell line showed specific, saturable binding of an SS analogue (MK-678) with high affinity for SSTR2 on cholangiocarcinoma membranes; inhibition in vitro of tumor cell proliferation by SS-14 and its analogue, octreotide; and inhibition in vivo of tumor growth in athymic mice implanted with human cholangiocarcinoma cells and treated with lanreotide, another SS analogue. Experiments to elucidate a possible mechanism of growth inhibition by SS showed it was not through changes in cellular cyclic adenosine monophosphate or calcium levels. Using gamma camera imaging with an 111In- SS analogue, we localized a histologically proven cholangiocarcinoma in a patient. CONCLUSIONS: These results suggest that SS analogues may be useful for diagnostic localization and treatment of biliary tract malignancies.[1]References
- Human cholangiocarcinomas express somatostatin receptors and respond to somatostatin with growth inhibition. Tan, C.K., Podila, P.V., Taylor, J.E., Nagorney, D.M., Wiseman, G.A., Gores, G.J., LaRusso, N.F. Gastroenterology (1995) [Pubmed]
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