Gastric carcinogenesis and the cancer stem cell hypothesis

Yoshiro Saikawa, Kazumasa Fukuda, Tsunehiro Takahashi, Rieko Nakamura, Hiroya Takeuchi, Yuko Kitagawa

Research output: Contribution to journalReview article

52 Citations (Scopus)

Abstract

Normal stem cells (NSCs) are reported to exist in most tissues, including the brain, bone marrow, and probably the gastrointestinal tract. In the latter case, they are thought to possess both the self-renewal capacity and asymmetrical division capacity to generate progenitor cells which differentiate into epithelial cells. NSCs in the normal gastric mucosa are thought to be present in the proliferative zone of the neck/isthmus region, and to undergo a complex bipolar migration from the neck/isthmus region either upward or downward, becoming differentiated normal epithelial cells. NSCs in human gastric mucosa are difficult to identify due to the current lack of a useful marker. A precise definition of cancer stem cells (CSCs) is still under discussion. CSCs are generally defined as malignant cells with NSC capacity. However, many studies of CSCs have demonstrated their rapid growth and high metastatic potential, while NSCs are thought to be slow-growing and self-renewing, and to lack functional capacities such as cell migration and attachment. Recent evidence suggests the existence of CSCs in a wide variety of solid tumors. In this review, we will discuss the existence and cell biology of gastric NSCs and CSCs. We will also discuss whether gastric CSCs originate as organ-specific stem cells or as bone marrow-derived cells (BMDCs). Under certain conditions, the local microenvironment may promote the development of gastric cancer. Thus, Helicobacter pylori infection and the accompanying chronic inflammatory processes will supply critical initiators inducing cell growth and the tissue repair response, leading to carcinogenesis. This mechanism will be discussed in light of stem cell research. Progress in stem cell research in the gastric field is still limited to experimental animal models. However, recent studies should enhance our understanding of human cancer biology, and provide novel tools for the treatment of incurable gastric cancer.

Original languageEnglish
Pages (from-to)11-24
Number of pages14
JournalGastric Cancer
Volume13
Issue number1
DOIs
Publication statusPublished - 2010 Mar 1

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Keywords

  • Cancer stem cell
  • Gastric cancer

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

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