Gastrointestinal hormone receptors in primary human colorectal carcinomas

Celia Chao, Marsha L. Tallman, Kirk L. Ives, Courtney Townsend, Mark Hellmich

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background. In this study, the prevalence and identity of the cells expressing functional receptors for the gastrointestinal (GI) peptide hormones: gastrin, bombesin, and neurotensin in dissociated cells from 20 freshly resected human primary colorectal carcinomas were determined. Materials and methods. GI peptide hormone-induced increases in the concentration of free intracellular Ca2+ ([Ca2+]i) were used as an assay for the detection of functional receptors. Reverse-transcription polymerase chain reaction (RT-PCR) was performed in a subset of tumor samples. Agonist-responsive cells were identified as either of epithelial or stromal origin by immunocytochemistry with cytokeratin and vimentin antibodies, respectively. Results. Overall, expression of GI peptide hormone receptors was more frequent in stromal cells when compared to epithelial cells. Of the three receptors, expression of bombesin receptor (95%) was most prevalent in vimentin-positive (stromal) cells; whereas, gastrin receptor expression by cytokeratin-positive (epithelial) cells was more common (39%). A single gastrin receptor splice variant differentially regulates [Ca2+]i in a cell-type specific manner. The gastrin receptor-expression profile in the 11 colon cancer-derived cell lines did not reflect the prevalence of expression in primary human cancers. Conclusions. The Ca2+ assay is a sensitive method for detecting functional GI peptide hormone receptor expression by colon cancer cells. Because this approach utilizes living cells, it is amenable to further functional analyses of signal transduction mechanisms at the single cell level. Importantly, our data provide a rationale for examining of the role of these GI peptide hormones and their cognate receptors in mesenchymal cell biology.

Original languageEnglish (US)
Pages (from-to)313-321
Number of pages9
JournalJournal of Surgical Research
Volume129
Issue number2
DOIs
StatePublished - Dec 2005

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Gastrointestinal Hormone Receptors
Colorectal Neoplasms
Cholecystokinin B Receptor
Peptide Receptors
Gastrointestinal Hormones
Peptide Hormones
Vimentin
Stromal Cells
Keratins
Colonic Neoplasms
Epithelial Cells
Bombesin Receptors
Bombesin
Neurotensin
Gastrins
Reverse Transcription
Cell Biology
Signal Transduction
Neoplasms
Immunohistochemistry

Keywords

  • Bombesin
  • Colorectal cancer
  • Epithelial cells
  • Gastrin
  • Neurotensin
  • Stromal cells

ASJC Scopus subject areas

  • Surgery

Cite this

Gastrointestinal hormone receptors in primary human colorectal carcinomas. / Chao, Celia; Tallman, Marsha L.; Ives, Kirk L.; Townsend, Courtney; Hellmich, Mark.

In: Journal of Surgical Research, Vol. 129, No. 2, 12.2005, p. 313-321.

Research output: Contribution to journalArticle

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abstract = "Background. In this study, the prevalence and identity of the cells expressing functional receptors for the gastrointestinal (GI) peptide hormones: gastrin, bombesin, and neurotensin in dissociated cells from 20 freshly resected human primary colorectal carcinomas were determined. Materials and methods. GI peptide hormone-induced increases in the concentration of free intracellular Ca2+ ([Ca2+]i) were used as an assay for the detection of functional receptors. Reverse-transcription polymerase chain reaction (RT-PCR) was performed in a subset of tumor samples. Agonist-responsive cells were identified as either of epithelial or stromal origin by immunocytochemistry with cytokeratin and vimentin antibodies, respectively. Results. Overall, expression of GI peptide hormone receptors was more frequent in stromal cells when compared to epithelial cells. Of the three receptors, expression of bombesin receptor (95{\%}) was most prevalent in vimentin-positive (stromal) cells; whereas, gastrin receptor expression by cytokeratin-positive (epithelial) cells was more common (39{\%}). A single gastrin receptor splice variant differentially regulates [Ca2+]i in a cell-type specific manner. The gastrin receptor-expression profile in the 11 colon cancer-derived cell lines did not reflect the prevalence of expression in primary human cancers. Conclusions. The Ca2+ assay is a sensitive method for detecting functional GI peptide hormone receptor expression by colon cancer cells. Because this approach utilizes living cells, it is amenable to further functional analyses of signal transduction mechanisms at the single cell level. Importantly, our data provide a rationale for examining of the role of these GI peptide hormones and their cognate receptors in mesenchymal cell biology.",
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