Heterogeneity in mouse spasmolytic polypeptide-expressing metaplasia lineages identifies markers of metaplastic progression

Victoria G. Weis, Josane F. Sousa, Bonnie J. LaFleur, Ki Taek Nam, Jared A. Weis, Paul E. Finke, Nadia A. Ameen, James G. Fox, James R. Goldenring

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Objectives Spasmolytic polypeptide-expressing metaplasia (SPEM) develops as a preneoplastic lesion in the stomachs of mice and humans after parietal cell loss. To identify the commonalities and differences between phenotypic SPEM lineages, SPEM were studied from three different mouse models of parietal cell loss: with chronic inflammation with Helicobacter felis infection; with acute inflammation with L635 treatment; and without inflammation following DMP-777 treatment. Design RNA transcripts from laser capture microdissected normal chief cells and SPEM lineages were compared using gene microarray. Alterations in transcripts were validated by quantitative real-time PCR. Clusterin and cystic fibrosis transmembrane conductance regulator (CFTR) were selected for immunohistochemical analysis in all mouse models as well as in human SPEM, intestinal metaplasia and gastric cancer. Results Transcript expression patterns demonstrated differences among the phenotypic SPEM models. Clusterin expression was significantly upregulated in all three mouse SPEM models as well as in human SPEM. The highest clusterin expression in human gastric cancers correlated with poor survival. Conversely, CFTR expression was upregulated only in SPEM with inflammation in mice. In humans, intestinal metaplasia, but not SPEM, expressed CFTR. Conclusions While markers such as clusterin are expressed in all phenotypic SPEM lineages, distinct patterns of upregulated genes including CFTR are present in murine metaplasia associated with inflammation, indicative of progression of metaplasia towards a more intestinalised metaplastic phenotype.

Original languageEnglish
Pages (from-to)1270-1279
Number of pages10
JournalGut
Volume62
Issue number9
DOIs
Publication statusPublished - 2013 Sep 1

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Metaplasia
Clusterin
Cystic Fibrosis Transmembrane Conductance Regulator
Inflammation
DMP 777
spasmolytic polypeptide
Stomach Neoplasms
Helicobacter felis
Intestinal Neoplasms
Helicobacter Infections
Genes
Real-Time Polymerase Chain Reaction
Stomach

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Weis, V. G., Sousa, J. F., LaFleur, B. J., Nam, K. T., Weis, J. A., Finke, P. E., ... Goldenring, J. R. (2013). Heterogeneity in mouse spasmolytic polypeptide-expressing metaplasia lineages identifies markers of metaplastic progression. Gut, 62(9), 1270-1279. https://doi.org/10.1136/gutjnl-2012-302401
Weis, Victoria G. ; Sousa, Josane F. ; LaFleur, Bonnie J. ; Nam, Ki Taek ; Weis, Jared A. ; Finke, Paul E. ; Ameen, Nadia A. ; Fox, James G. ; Goldenring, James R. / Heterogeneity in mouse spasmolytic polypeptide-expressing metaplasia lineages identifies markers of metaplastic progression. In: Gut. 2013 ; Vol. 62, No. 9. pp. 1270-1279.
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abstract = "Objectives Spasmolytic polypeptide-expressing metaplasia (SPEM) develops as a preneoplastic lesion in the stomachs of mice and humans after parietal cell loss. To identify the commonalities and differences between phenotypic SPEM lineages, SPEM were studied from three different mouse models of parietal cell loss: with chronic inflammation with Helicobacter felis infection; with acute inflammation with L635 treatment; and without inflammation following DMP-777 treatment. Design RNA transcripts from laser capture microdissected normal chief cells and SPEM lineages were compared using gene microarray. Alterations in transcripts were validated by quantitative real-time PCR. Clusterin and cystic fibrosis transmembrane conductance regulator (CFTR) were selected for immunohistochemical analysis in all mouse models as well as in human SPEM, intestinal metaplasia and gastric cancer. Results Transcript expression patterns demonstrated differences among the phenotypic SPEM models. Clusterin expression was significantly upregulated in all three mouse SPEM models as well as in human SPEM. The highest clusterin expression in human gastric cancers correlated with poor survival. Conversely, CFTR expression was upregulated only in SPEM with inflammation in mice. In humans, intestinal metaplasia, but not SPEM, expressed CFTR. Conclusions While markers such as clusterin are expressed in all phenotypic SPEM lineages, distinct patterns of upregulated genes including CFTR are present in murine metaplasia associated with inflammation, indicative of progression of metaplasia towards a more intestinalised metaplastic phenotype.",
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Weis, VG, Sousa, JF, LaFleur, BJ, Nam, KT, Weis, JA, Finke, PE, Ameen, NA, Fox, JG & Goldenring, JR 2013, 'Heterogeneity in mouse spasmolytic polypeptide-expressing metaplasia lineages identifies markers of metaplastic progression', Gut, vol. 62, no. 9, pp. 1270-1279. https://doi.org/10.1136/gutjnl-2012-302401

Heterogeneity in mouse spasmolytic polypeptide-expressing metaplasia lineages identifies markers of metaplastic progression. / Weis, Victoria G.; Sousa, Josane F.; LaFleur, Bonnie J.; Nam, Ki Taek; Weis, Jared A.; Finke, Paul E.; Ameen, Nadia A.; Fox, James G.; Goldenring, James R.

In: Gut, Vol. 62, No. 9, 01.09.2013, p. 1270-1279.

Research output: Contribution to journalArticle

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T1 - Heterogeneity in mouse spasmolytic polypeptide-expressing metaplasia lineages identifies markers of metaplastic progression

AU - Weis, Victoria G.

AU - Sousa, Josane F.

AU - LaFleur, Bonnie J.

AU - Nam, Ki Taek

AU - Weis, Jared A.

AU - Finke, Paul E.

AU - Ameen, Nadia A.

AU - Fox, James G.

AU - Goldenring, James R.

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N2 - Objectives Spasmolytic polypeptide-expressing metaplasia (SPEM) develops as a preneoplastic lesion in the stomachs of mice and humans after parietal cell loss. To identify the commonalities and differences between phenotypic SPEM lineages, SPEM were studied from three different mouse models of parietal cell loss: with chronic inflammation with Helicobacter felis infection; with acute inflammation with L635 treatment; and without inflammation following DMP-777 treatment. Design RNA transcripts from laser capture microdissected normal chief cells and SPEM lineages were compared using gene microarray. Alterations in transcripts were validated by quantitative real-time PCR. Clusterin and cystic fibrosis transmembrane conductance regulator (CFTR) were selected for immunohistochemical analysis in all mouse models as well as in human SPEM, intestinal metaplasia and gastric cancer. Results Transcript expression patterns demonstrated differences among the phenotypic SPEM models. Clusterin expression was significantly upregulated in all three mouse SPEM models as well as in human SPEM. The highest clusterin expression in human gastric cancers correlated with poor survival. Conversely, CFTR expression was upregulated only in SPEM with inflammation in mice. In humans, intestinal metaplasia, but not SPEM, expressed CFTR. Conclusions While markers such as clusterin are expressed in all phenotypic SPEM lineages, distinct patterns of upregulated genes including CFTR are present in murine metaplasia associated with inflammation, indicative of progression of metaplasia towards a more intestinalised metaplastic phenotype.

AB - Objectives Spasmolytic polypeptide-expressing metaplasia (SPEM) develops as a preneoplastic lesion in the stomachs of mice and humans after parietal cell loss. To identify the commonalities and differences between phenotypic SPEM lineages, SPEM were studied from three different mouse models of parietal cell loss: with chronic inflammation with Helicobacter felis infection; with acute inflammation with L635 treatment; and without inflammation following DMP-777 treatment. Design RNA transcripts from laser capture microdissected normal chief cells and SPEM lineages were compared using gene microarray. Alterations in transcripts were validated by quantitative real-time PCR. Clusterin and cystic fibrosis transmembrane conductance regulator (CFTR) were selected for immunohistochemical analysis in all mouse models as well as in human SPEM, intestinal metaplasia and gastric cancer. Results Transcript expression patterns demonstrated differences among the phenotypic SPEM models. Clusterin expression was significantly upregulated in all three mouse SPEM models as well as in human SPEM. The highest clusterin expression in human gastric cancers correlated with poor survival. Conversely, CFTR expression was upregulated only in SPEM with inflammation in mice. In humans, intestinal metaplasia, but not SPEM, expressed CFTR. Conclusions While markers such as clusterin are expressed in all phenotypic SPEM lineages, distinct patterns of upregulated genes including CFTR are present in murine metaplasia associated with inflammation, indicative of progression of metaplasia towards a more intestinalised metaplastic phenotype.

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