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Correspondence re: Weinberg et al., Cholecystokinin and Gastrin Levels Are Not Elevated in Pancreatic Carcinoma. Cancer Epidemiol. Biomark. Prev., 10: 721–722, 2001

The University of Nottingham Cancer Studies Unit, University Hospital, Nottingham NG7 2UH, United Kingdom

The conclusions drawn by the authors are misleading due to a number of reasons:

(a) It is not clear what gastrin species were measured in their assay system. Many authors have shown that when confounding factors such as Helicobacter pylori infection and use of proton pump inhibitors are taken into account, there is no rise in amidated gastrin levels [Penman et al. (1) and Ciccotosto et al. (2) ]. However immature forms of gastrin, such as progastrin, are increased in colorectal cancer patients and have been shown to decrease following surgical resection of the tumor [Ciccotosto et al. (2) and Siddheshwar et al. (3) ].

(b) Pancreatic cancer has been shown by a number of groups to secrete immature gastrin forms and have a potential autocrine/paracrine pathway [Caplin et al. (4) , Smith et al. (5) , Goetze et al. (6) ], and it is therefore likely that such gastrin peptides are elevated in the serum.

(c) Interestingly, expression of both cholecystokinin and gastrin gene was shown both to be up-regulated in a gastric carcinoma cell line, with the gastrin gene being selectively transcribed [Goetze et al. (6) and van Solinge et al. (7) ]. This suggests that cholecystokinin protein secretion by malignant cells is unlikely to contribute to serum levels.

Footnotes

¹ To whom requests for reprints should be addressed, at Cancer Studies Unit, D Floor, West Block, Queens Medical Centre University Hospital, Nottingham NG7 2UH, United Kingdom.

Received 8/24/01; revised 8/24/01; accepted 11/16/01.

References

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2. Ciccotosto G. D., McLeish A., Hardy K., Shulkes A. Expression, processing and secretion of gastrin in patients with colorectal carcinoma. Gastroenterology, 109: 1142-1153, 1995.[Medline]
3. Siddheshwar R. K., Gray J. C., Kelly S. B. Plasma levels of progastrin but not amidated gastrin or glycine extended gastrin are elevated in patients with colorectal carcinoma. Gut, 48: 47-52, 2001.[Abstract/Free Full Text]
4. Caplin M. E., Clarke P., Grimes S., Dhillon A. P., Khan K., Savage K., Lewin J., Michaeli D., Pounder R. E., Watson S. A. Demonstration of new sites of expression of the CCK-B/gastrin receptor in pancreatic acinar AR42J cells using immunoelectron microscopy. Regul. Pept., 84: 81-89, 1999.[Medline]
5. Smith J. P., Shih A., Wu Y., McLaughlin P. J., Zagon I. S. Gastrin regulates growth of human pancreatic cancer in a tonic and autocrine fashion. Am. J. Physiol., 270: 878-874, 1996.
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7. van Solinge W. W., Rehfeld J. F. Co-transcription of the gastrin and cholecystokinin genes with selective translation of gastrin mRNA in a human gastric carcinoma cell line. FEBS Lett., 309: 47-50, 1992.[Medline]

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