Human cholangiocarcinomas express somatostatin receptors and respond to somatostatin with growth inhibition.
OBJECTIVE
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.
Tan
C K
CK
Center for Basic Research in Digestive Diseases, Mayo Medical School, Clinic, and Foundation, Rochester, Minnesota, USA.
Podila
P V
PV
Taylor
J E
JE
Nagorney
D M
DM
Wiseman
G A
GA
Gores
G J
GJ
LaRusso
N F
NF
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000737:chemistry* / Q000175:diagnosis / Q000188:drug therapy; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D017481:Receptors, Somatostatin / Q000032:analysis* / Q000235:genetics; D013004:Somatostatin / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; D000242:Cyclic AMP; D002118:Calcium