Expression, processing, and secretion of gastrin in patients with colorectal carcinoma.
OBJECTIVE
The relationship between gastrin and the development of colorectal carcinoma (CRC) remains controversial. Problems with previous studies include failure to measure all forms of gastrin, lack of comparison between stored and secreted gastrin, and not controlling for Helicobacter pylori infection (a known cause of hypergastrinemia). The aim of this study was to quantify progastrin and progastrin-derived peptides in the resected tumor and plasma of patients with CRC and in the antrum and plasma of normal subjects.


METHODS
Four region-specific gastrin antisera were used to measure progastrin, glycine-extended gastrin, amidated gastrin, and total gastrin.


RESULTS
Progastrin, amidated gastrin, total gastrin, and glycine-extended gastrin were detected in 100%, 69%, 56%, and 44% of tumors, respectively (n = 32). When allowing for H. pylori infection, circulating amidated gastrin levels were not significantly elevated in patients with CRC. However, compared with control H. pylori-positive and H. pylori-negative subjects, fasting plasma total gastrin levels were increased in H. pylori-positive (5.2-fold) and H. pylori-negative (2.3-fold) patients with CRC.


CONCLUSIONS
Gastrin or its processing intermediates are present in a high proportion of CRCs. Nonamidated gastrin levels are elevated in the circulation of patients with CRC regardless of H. pylori status. We conclude that gastrin should continue to be assessed as a circulating or autocrine growth factor in the development of CRC.
Ciccotosto
G D
GD
Department of Surgery, University of Melbourne, Victoria, Australia.
McLeish
A
A
Hardy
K J
KJ
Shulkes
A
A
D000368:Aged; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005755:Gastrins / Q000096:biosynthesis* / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D011498:Protein Precursors / Q000378:metabolism; D011706:Pyloric Antrum / Q000737:chemistry
D005755:Gastrins; D011498:Protein Precursors; C086854:glycine-extended gastrin 17; C013706:big gastrin