Gastric stem cells and gastric cancer stem cells

Anatomy & cell biology 03/2013; 46(1):8. DOI: 10.5115/acb.2013.46.1.8


The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal evolution hypothesis, only cancer stem cells can initiate tumor formation, self-renew, and differentiate into various kinds of daughter cells. Because gastric cancer can originate from gastric stem cells and their self-renewal mechanism can be used by gastric cancer stem cells, we review here how critical signaling pathways, including hedgehog, Wnt, Notch, epidermal growth factor, and bone morphogenetic protein signaling, may regulate the self-renewal and differentiation of gastric stem cells and gastric cancer stem cells. In addition, the precancerous change of the gastric epithelium and the status of isolating gastric cancer stem cells from patients are reviewed.

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    • "CSCs population is identified and purified by specific cell surface markers. Among different markers, CD44 is widely used for isolation of CSCs from solid tumors [3] .CD44 is a trans‐membrane glycoprotein, which plays important roles in malignant behavior of several human cancers and it was reported as a cell surface marker to identify gastric cancer stem cells in gastric cancer cell lines [12] [24] [25] . "
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    ABSTRACT: Cancer stem cells (CSCs) have been defined as a unique subpopulation in tumors, endowed with the capacity to initiate tumor progression, and maintain self‐renewal as well as metastatic potential. Recently, more evidences strongly indicate the existence of CSCs in solid tumors of wide variety of organs such as breast, brain and stomach. Recent studies suggest that a special subpopulation of gastric cancer cells with specific marker namely CD44, shows spheroid colony formation in serum free media in vitro, as well as tumorigenic capacity in immunodeficient animal model in vivo. In addition, current evidences indicate that one of the major reasons for failure of chemotherapy and radiotherapy is the existence of CSCs with resistant mechanisms against current therapeutic strategies. Growing evidence recommended that pathways which are responsible for regulation of normal stem cell self‐renewal and differentiation may also represent regulatory roles in maintenance of cancer cells and CSCs. Two major therapeutic approaches for elimination of CSCs are differentiation therapy and inhibition of important pathways involved in maintenance of CSCs such as notch signaling.It is hypothesized that with inhibition of notch signaling by means of DAPT(gamma‐secretase‐inhibitor), silencing Ral pathway as well as inducing differentiation by means of all‐trance retinoic acid (ATRA) in CD44+ gastric cancer stem cells, we can target this small population and eventually eliminate them by sensitizing these cells to chemotherapy and radiotherapy as well as induction of apoptosis in them.
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    07/2013; 5(3):61-7. DOI:10.4252/wjsc.v5.i3.61
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    ABSTRACT: Gastric cancer is one of the most outgoing human cancers in the world. Two main functional types were described: Intestinal adenocarcinoma and diffuse one. The most important purpose of this review is to analyze and investigate the main genetic factors involved in tumorogenesis of stomach and the molecular mechanism of their expression regulation alongside with the importance of cancer stem cells and their relationship with gastric cancer. It is evident that proper diagnosis of molecular case of cancer may lead to absolute treatment and at least reduction in the disease severity. However, stemness factors such as Sox2, Oct3/4, and Nanog were related with induced pluripotent stem cells, proposing a correlation between these stemness factors and cancer stem cells. Moreover, aberrant induction by Helicobacter pylori of the intestinal-specific homeobox transcription factors, CDX1 and CDX2, also plays an important role in this modification. There are some genes which are directly activated by CDX1 in gastric cancer and distinguished stemness-related reprogramming factors like SALL4 and KLF5. Correspondingly, we also aimed to present the main important epigenetic changes such as DNA methylation, histone modification, and chromatin modeling of stemness genes in disease development. Remarkably, a better understanding of molecular bases of cancer may lead to novel diagnostic, therapeutic, and preventive approaches by some genetic and epigenetic changes such as gene amplifications, gene silencing by DNA methylation, losses of imprinting, LOH, and mutations. Consequently, genome-wide searches of gene expression are widely important for surveying the proper mechanisms of cancer emergence and development. Conspicuously, this review explains an outline of the molecular mechanism and new approaches in gastric cancer.
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