Gastric cancer stem cells: therapeutic targets

Abstract

During the past decade, a growing body of evidence has implied that cancer stem cells (CSCs) play an important role in the development of gastric cancer (GC). The notion that CSCs give rise to GC and may be responsible for invasion, metastasis, and resistance to treatment has profound implications for anti-cancer therapy. Recent major advances in the rapidly evolving field of CSCs have opened novel exciting opportunities for developing CSC-targeted therapies. Discovery of specific markers and signaling pathways in gastric CSCs (GCSCs), with the perfecting of technologies for identification, isolation, and validation of CSCs, may provide the basis for a revolutionary cancer treatment approach based on the eradication of GCSCs. Emerging therapeutic tools based on specific properties and functions of CSCs, including activation of self-renewal signaling pathways, differences in gene expression profiles, and increased activity of telomerase or chemoresistance mechanisms, are developing in parallel with advances in nanotechnology and bioengineering. The addition of GCSC-targeted therapies to current oncological protocols and their complementary application may be the key to successfully fighting GC.

Prognostic significance of leucine-rich-repeat-containing G-protein-coupled receptor 5, an intestinal stem cell marker, in gastric carcinomas

“…For instance, myofibroblasts expressing a high level of hepatocyte growth factor can activate Wnt signaling and even restore the stem cell phenotype in more differentiated tumor cells [38]. The Hedgehog and Notch pathways are also known to be deeply involved in the cancer stem cell properties [4]. Thus, our results suggest that LGR5 overexpression alone is not sufficient to recapitulate the molecular characteristics of LGR5-positive cells in GC.…”

“…Rapidly mounting evidence suggests that cancer stem cells not only maintain tumor growth but also result in relapse after therapy, suggesting they could be a candidate for new targeted therapy [4]. Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) has been demonstrated as a global stem cell marker in multiple organs, including the small intestine, colon, stomach, hair follicle, kidney, ovary, liver, and mammary gland [5][6][7][8][9][10][11].…”

Sulforaphane improves chemotherapy efficacy by targeting cancer stem cell-like properties via the miR-124/IL-6R/STAT3 axis

“…Tumor cells have heterogeneity and the less-differentiated CSCs are recognized as the origin of tumorigenesis, metastasis and recurrence in numerous human cancers1632. Gastric CSCs have been isolated in several cell lines as well as in primary tumors1933. Our results showed that CDDP elevated the ratios of SP and CD44 + /EpCAM + cells in a dose-dependent manner.…”

“…There are mainly three methods for the identification of CSCs or CSC-like properties: (1) use of CSCs surface markers, such as CD44 + CD24 − , CD133, CD44 + /EpCAM + , and CD901718; (2) identifying the side population (SP) in cancer cells, which enriches CSC-like properties; and (3) determining the growth properties of cells in serum-free suspension culture19. Here, in GC cells, we validated that, CDDP elevated the ratios of SP and CD44 + /EpCAM + cells in a dose-dependent manner (Fig.…”

Genomic landscape of gastric cancer: molecular classification and potential targets

“…Transforming growth factor  (TGF-), Wnt and hedgehog signaling are pivotal pathways that influence the cell division, invasion, migration and ulcer repair processes Lagasse, 2008;Zhao, 2014). Disorders in these processes usually lead to gastric adenocarcinoma and other tissue-specific gastrointestinal cancers (Stojnev et al, 2014). Genome sequencing and comprehensive molecular profiling have identified novel driver mutations involved in stem cell pathways in gastric cancer.…”