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The role of gastrin and CCK-B/gastrin receptor in hepatocellular and pancreatic cancers

The role of gastrin and CCK-B/gastrin receptor in hepatocellular and pancreatic cancers
The role of gastrin and CCK-B/gastrin receptor in hepatocellular and pancreatic cancers

The in vitro effects of gastrin, glycine-extended gastrin, anti-gastrin antibodies and the CCK-B receptor antagonist PD135,158 were assessed on hepatoma cell lines. This study demonstrated that amidated gastrin and glycine-extended gastrin stimulated some hepatoma cell lines and that this could be abrogated by anti-gastrin agents.

Tissue sections from patients with hepatocellular carcinoma, fibrolamellar carcinoma, cholangiocarcinoma as well as normal liver biopsies were assessed for expression of CCK-B receptor and gastrin isoforms. The results showed that most liver tumours express CCK-B receptor and precursor forms of gastrin. There appears to be little expression of the receptor and no expression of precursor forms of gastrin in normal liver.

Tissue sections from patients with pancreatic cancer and normal pancreas were assessed for expression of CCK-B receptor and gastrin isoforms. The results showed that the normal pancreas showed no expression of receptor or gastrin isoforms except for occasional cells in the islets. The pancreatic cancer patients showed definite expression of CCK-B receptor and predominantly precursor forms of cancer.

Studies were performed to identify the cellular sites of expression of the CCK-B receptor in the known CCK-B receptor bearing pancreatic acinar AR42J cells. Using immunoelectron microscopy and western blotting techniques the CCK-B receptor was shown to be expressed not only on the cell membrane, but also in the cytoplasm and nucleus of cells.

In conclusion the expression of the gastrin precursor forms is most likely related to the autocrine production of gastrin by cancer cells. The nuclear expression of the receptor is a novel finding and may contribute to cellular proliferation in cancer cells. Gastrin and its receptor appear to be important in the growth of a variety of cancers and the understanding of this proliferative effect has led to the development of anti-gastrin agents now undergoing therapeutic clinical trials in gastrointestinal and pancreatic cancers.

University of Southampton
Caplin, Martyn Evan
b00b4bdb-ebb1-45d9-9cd7-054c00ad2d4c
Caplin, Martyn Evan
b00b4bdb-ebb1-45d9-9cd7-054c00ad2d4c

Caplin, Martyn Evan (2002) The role of gastrin and CCK-B/gastrin receptor in hepatocellular and pancreatic cancers. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

The in vitro effects of gastrin, glycine-extended gastrin, anti-gastrin antibodies and the CCK-B receptor antagonist PD135,158 were assessed on hepatoma cell lines. This study demonstrated that amidated gastrin and glycine-extended gastrin stimulated some hepatoma cell lines and that this could be abrogated by anti-gastrin agents.

Tissue sections from patients with hepatocellular carcinoma, fibrolamellar carcinoma, cholangiocarcinoma as well as normal liver biopsies were assessed for expression of CCK-B receptor and gastrin isoforms. The results showed that most liver tumours express CCK-B receptor and precursor forms of gastrin. There appears to be little expression of the receptor and no expression of precursor forms of gastrin in normal liver.

Tissue sections from patients with pancreatic cancer and normal pancreas were assessed for expression of CCK-B receptor and gastrin isoforms. The results showed that the normal pancreas showed no expression of receptor or gastrin isoforms except for occasional cells in the islets. The pancreatic cancer patients showed definite expression of CCK-B receptor and predominantly precursor forms of cancer.

Studies were performed to identify the cellular sites of expression of the CCK-B receptor in the known CCK-B receptor bearing pancreatic acinar AR42J cells. Using immunoelectron microscopy and western blotting techniques the CCK-B receptor was shown to be expressed not only on the cell membrane, but also in the cytoplasm and nucleus of cells.

In conclusion the expression of the gastrin precursor forms is most likely related to the autocrine production of gastrin by cancer cells. The nuclear expression of the receptor is a novel finding and may contribute to cellular proliferation in cancer cells. Gastrin and its receptor appear to be important in the growth of a variety of cancers and the understanding of this proliferative effect has led to the development of anti-gastrin agents now undergoing therapeutic clinical trials in gastrointestinal and pancreatic cancers.

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Published date: 2002

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Local EPrints ID: 465082
URI: http://eprints.soton.ac.uk/id/eprint/465082
PURE UUID: 813a35a5-aeed-4651-9f6c-5073fb6f9440

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Date deposited: 05 Jul 2022 00:22
Last modified: 23 Jul 2022 01:13

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Author: Martyn Evan Caplin

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