Functional role of <scp>CD</scp>44v‐x<scp>CT</scp> system in the development of spasmolytic polypeptide‐expressing metaplasia

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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“…33 CD44v9 staining was found in the basolateral membrane in 32% of cells at the base of the first gland (Fig. 2, Table 2).…”

Section: Resultsmentioning

confidence: 94%

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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“…26,27 Furthermore, CD44v expression was increased in these gastric tumor cells, and inhibition of cystine transport by system xc(−) with sulfasalazine, an inhibitor of xCT-dependent cystine transport, suppressed the development of gastric tumors in these transgenic mice. 28 Our findings revealed that targeted therapy against the CD44v-xCT system may provide a strategy for targeting CSCs in GC treatment. However, a recent study indicated …”

Section: Critical Analysis Of the Potential For Targeting Cscs In Gcmentioning

confidence: 72%

Targeting cancer stem cells in gastric cancer

Ishimoto¹,

Baba²

2014

GICTT

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Gastric cancer (GC) remains a leading cause of cancer-related deaths worldwide. Despite the recent advance of anticancer drugs and the development of molecular-targeted drugs, the prognosis of patients with advanced GC remains poor, especially in Western countries, and is mainly implicated in tumor relapse and metastasis. Cancer stem cells are selectively capable of tumor initiation and implicated in tumor relapse and metastasis, thus governing the prognosis of GC patients. Recent investigations have indicated that gastric cancer stem cells (GCSCs) are likely to be the most crucial target in GC treatments. Therefore, the identification of key molecules related to GCSCs is expected to contribute toward the extermination of GC. This review presents the current molecular-targeted therapies against GC according to recent clinical trials and the findings regarding GCSCs and their maintenance that will enable the development of novel therapeutic strategies for patients with GC.

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“…Moreover, we found that CD44v expression was upregulated in these gastric tumor cells. We also showed that the inhibition of the cystine transport system xc(-) with sulfasalazine, an inhibitor of xCT-dependent cystine transport, suppressed the progression of gastric tumors in these transgenic mice [55] . Our findings suggest that targeted therapy against the CD44v-xCT system may provide a strategy for the targeting of CD44v positive GCSCs.…”

Section: Current Treatment Of Gc and The Potential For Targeting Gcscsmentioning

confidence: 74%

Therapeutic targets against gastric cancer stem cells interacting with tumor microenvironment

Uchihara¹,

Ishimoto²,

Yonemura³

et al. 2018

JCMT

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Gastric cancer (GC) is a major cause of cancer-related deaths worldwide. The existence of cancer stem cells (CSCs) is known to be the main reason for resistance to anticancer agents as well as for the development of distant metastases. Although CSCs themselves harbor self-renewal and differentiation abilities, the tumor microenvironment that surrounds CSCs provides secreted factors and supports angiogenesis and is thus responsible for the maintenance of their CSC properties. The current review provides information regarding the impact of the tumor microenvironment on gastric CSCs, which will support the development of novel therapeutic strategies for targeting gastric CSCs.

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Functional role of CD44v‐xCT system in the development of spasmolytic polypeptide‐expressing metaplasia

Cited by 82 publications

References 34 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

Targeting cancer stem cells in gastric cancer

Therapeutic targets against gastric cancer stem cells interacting with tumor microenvironment

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