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

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

doi:10.1136/gutjnl-2012-302401

Cited by 98 publications

(128 citation statements)

References 32 publications

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“…Clusterin is considered a stress response protein and has been associated with metaplastic lineages in the stomach such as SPEM. 31 The first gland cells also prominently expressed both MUC4 and Sox2, which were not significantly expressed in the corpus and antrum, but are observed in SPEM. 31 Thus, the patterns of lineage expression show aspects of SPEM, suggesting that the first gland could have characteristics of a reparative metaplasia.…”

Section: Discussionmentioning

confidence: 99%

“…31 The first gland cells also prominently expressed both MUC4 and Sox2, which were not significantly expressed in the corpus and antrum, but are observed in SPEM. 31 Thus, the patterns of lineage expression show aspects of SPEM, suggesting that the first gland could have characteristics of a reparative metaplasia. Given the high expression of Clusterin and the presence of large numbers of chemosensory cells in the first gland, it is tempting to hypothesize that the first gland may represent a source for reparative lineages in the proximal stomach.…”

Section: Discussionmentioning

confidence: 99%

“…36,[38][39][40] MUC4 is upregulated in SPEM in rodent models. 31,41 MUC4 staining revealed 47.7% MUC4-expressing cells in the first gland, although there were no MUC4 positive cells in either the antrum or corpus (Fig. 5, Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…32 Clusterin is upregulated in the stomach in metaplastic SPEM cells. 31 Although only scattered Clusterin positive cells were observed in the neck region of the corpus mucosa, nearly 72% of the cells in the first gland immunostained for Clusterin (Fig. 4, Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…[28][29][30][31] We therefore examined gastric tissues with SPEM markers. Clusterin, also known as apolipoprotein J, has been implicated in many biological processes including oxidative stress, clearance of cellular debris, and inflammation.…”

Section: Resultsmentioning

confidence: 99%

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Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric Corpus

O’Neil

Petersen

Choi

et al. 2016

J Histochem Cytochem.

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SummaryThe glandular stomach has two major zones: the acid secreting corpus and the gastrin cell-containing antrum. Nevertheless, a single gland lies at the transition between the forestomach and corpus in the mouse stomach. We have sought to define the lineages that make up this gland unit at the squamocolumnar junction. The first gland in mice showed a notable absence of characteristic corpus lineages, including parietal cells and chief cells. In contrast, the gland showed strong staining of Griffonia simplicifolia-II (GSII)-lectin-positive mucous cells at the bases of glands, which were also positive for CD44 variant 9 and Clusterin. Prominent numbers of doublecortin-like kinase 1 (DCLK1) positive tuft cells were present in the first gland. The first gland contained Lgr5-expressing putative progenitor cells, and a large proportion of the cells were positive for Sox2. The cells of the first gland stained strongly for MUC4 and EpCAM, but both were absent in the normal corpus mucosa. The present studies indicate that the first gland in the corpus represents a unique anatomic entity. The presence of a concentration of progenitor cells and sensory tuft cells in this gland suggests that it may represent a source of reserve reparative cells for adapting to severe mucosal damage. (J Histochem Cytochem 65:47-58, 2017)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric Corpus

O’Neil

Petersen

Choi

et al. 2016

J Histochem Cytochem.

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Inhibition Lysosomal Degradation of Clusterin by Protein Kinase D3 Promotes Triple‐Negative Breast Cancer Tumor Growth

Liu

Zhou

et al. 2021

Advanced Science

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Triple negative breast cancer (TNBC), with its lack of targeted therapies, shows the worst mortality rate among all breast cancer subtypes. Clusterin (CLU) is implicated to play important oncogenic roles in cancer via promoting various downstream oncogenic pathways. Here, protein kinase D3 (PRKD3) is defined to be a key regulator of CLU in promoting TNBC tumor growth. Mechanically, PRKD3 with kinase activity binding to CLU is critical for CLU protein stability via inhibiting CLU's lysosomal distribution and degradation. CLU and PRKD3 protein level are significantly elevated and positively correlated in collected TNBC tumor samples. CLU silencer (OGX‐011) and PRKDs inhibitor (CRT0066101) can both result in impressive tumor growth suppression in vitro and in vivo, suggesting targeting CLU and its key regulator‐PRKD3 are promisingly efficient against TNBC. Finally, secreted CLU (sCLU) is found to be elevated in serums from TNBC patients and reduced in serum from TNBC murine models post OGX‐011 and/or CRT0066101 treatment, suggesting serum sCLU is a promising blood‐based biomarker for clinical management of TNBC. Taken together, this study provides a thorough molecular basis as well as preclinical evidences for targeting CLU pathway as a new promising strategy against TNBC via revealing PRKD3 as the key regulator of CLU in TNBC.

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Characterization of progressive metaplasia in the gastric corpus mucosa of Mongolian gerbils infected withHelicobacter pylori

et al. 2016

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Spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia are considered neoplastic precursors of gastric adenocarcinoma in humans. Loss of parietal cells causes the development of SPEM in the gastric corpus and then chronic inflammation drives SPEM toward a more proliferative lineage. Mongolian gerbils infected with Helicobacter pylori (H. pylori) develop chronic gastritis and metaplasia, mimicking aspects of human gastritis with H. pylori infection. We therefore examined metaplastic lineages in the gastric corpus mucosa of gerbils infected by H. pylori strain 7.13, which produces rapid onset of severe inflammation. Six weeks following H. pylori infection, Griffonia simplicifolia lectin II (GSII)-positive SPEM developed in the base of oxyntic glands in association with parietal cell loss and inflammation. In association with severe inflammation, SPEM glands evolved into aberrant phenotypes, including branched lesions, dilated lesions and penetrating invasive glands. Mucin 4 (MUC4) was upregulated in SPEM and progressive SPEM. Clusterin was expressed in the tips of branched and dilated lesions and throughout regions of invasive glands. Intriguingly, clusterin-positive regions in these lesions expressed Ki67 and matrix metalloproteinase 7 (MMP-7). These same regions were also positive for expression of phospho-IκBα, suggestive of activated NFκB signalling. These findings suggest that clusterin-positive regions in progressive phenotypes of SPEM have invasive characteristics. Thus, H. pylori infection in gerbils induces SPEM, which then can progress to further aberrant and invasive metaplastic phenotypes.

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

Cited by 98 publications

References 32 publications

Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric Corpus

Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric Corpus

Inhibition Lysosomal Degradation of Clusterin by Protein Kinase D3 Promotes Triple‐Negative Breast Cancer Tumor Growth

Characterization of progressive metaplasia in the gastric corpus mucosa of Mongolian gerbils infected withHelicobacter pylori

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