Gastric cancer stem cells: A novel therapeutic target

Abstract

Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer.

Identifying and targeting cancer stem cells in the treatment of gastric cancer

“…Specific cellular markers have been used to identify, isolate and therapeutically target CSCs 21, 22, 23. Several potential gastric CSC markers have been identified.…”

Inhibition of the peritoneal metastasis of human gastric cancer cells by dextran sulphate in vivo and in vitro

“…The metastasis of gastric cancer cells is a complex multistep process, involving invasion, adhesion, migration and other types of malignant biological behaviours (13). In particular, it involves three successive steps: i) Tumour invasion such that tumour cells leave the mucosa of the stomach; ii) migration of the non-adherent cancer cells into the abdominal cavity, where they adhere to the peritoneum; and iii) invasion and novel capillary formation with proliferation around the vasculature, with eventual formation of nodules of metastatic carcinoma (14). Positive staining for integrin β1 expression was observed in the cytoplasm.…”

“…Integrins comprise a transmembrane protein family composed of dimers of two subunits, α and β, and integrin β1 dimerises with different α subunits to constitute the vast majority of integrin complexes in the extracellular matrix (14). Integrins mainly function in two ways in the occurrence and development of tumours: i) Mediating the adhesion of tumour cells to the extracellular matrix by changing the composition of the substrate and adjusting the biological function of the matrix to promote the invasion and metastasis of tumour cells; and ii) mediating messages from the extracellular matrix to cells, as this information often affects cell growth and differentiation (14). The transfer of abnormal information by integrin promotes tumour cell growth, dedifferentiation and distant metastasis (15).…”

Therapeutic targets against gastric cancer stem cells interacting with tumor microenvironment

“…CSCs have subsequently been found in various types of solid tumors [10][11][12] . Gastric CSCs (GCSCs) have been vigorously investigated in studies using GC cell lines and primary GC tissues [13][14][15] .…”