**4. Conclusion**

To distinguish CSCs from other cancer cells, researchers have developed profiles of unique cellular markers. These profiles allow detection of CSCs within a tumor and enable the sepa-

ration of CSCs from nonstem cancer cells for *research purposes*.

**1.** surface markers (e.g., CD24, CD26, CD44, CD90, CD133, and CD166) [63].

**3.** formation of the spheres when cultured in nonadherent conditions [63].

gastric cancer initiation and progression in villin + gastric stem cells [66].

**4.** high tumorigenic potential when xenografted into immunocompromised mice.

The existence of CSCs in gastric cancer was first revealed by analyzing a panel of gastric cancer cell lines [64, 65]. Cancer stem cells from either gastric cancer cell lines or resected tumors were isolated using cell surface markers, such as CD44 and epithelial cell adhesion molecule (EpCAM) [65]. Moreover, gastric CSCs can even be isolated from the peripheral blood of gas-

Leucine-rich repeat containing G protein-coupled receptor-5 (Lgr5) is a gastric CSC marker

Stem cells that express villin exist in the pyloric gland and villin + gastric stem cells might be converted to gastric cancer cells [66]. Kruppel-like factor-4 (KLF4) might play a critical role in

In addition, ALDH1, CD90, CD71, and CD133 could be candidate markers of gastric CSCs. MicroRNAs might regulate the properties of gastric CSCs by inducing epithelial-mesenchy-

It must be noted, however, that no set of markers are exclusive to CSCs, and also that CSC phenotypes vary over time and between individual patients' tumors of the same subtype. These facts have caused researchers to speculate whether different clinical outcomes reflect

Multiple research findings indicate that conventional therapies, which target the rapidly dividing cells in tumors, have limited efficacy or even adverse effects on CSCs [30] and lead

Consequently, two types of cancer therapies targeting CSCs have been investigated: first, to induce and/or maintain dormancy of tumor cells, and second, to induce cell death in residual dormant cancer cells by targeting their markers. Consequently, gastric cancer therapies tar-

stem cells in the stomach could be the origin of gastric CSCs [66]. Patients with

cells have a short median survival [66].

Markers and characteristics of the cancer stem cells:

**2.** high aldehyde dehydrogenase (ALDH) activity [63].

tric cancer patients using CD44 and CD54.

gastric cancer containing Lgr5+

different CSC populations [63].

**3.10. Treatment of the cancer stem cells**

to treatment failure, chemoresistance, and recurrence.

geting CSCs have been investigated (**Table 3**) [70].

and Lgr5+

256 Gastric Cancer

mal transition [67].

Surgical treatment is not able to provide patients with GCLM a complete cure.

Advanced gastric cancer is one of the most difficult challenges in clinical practice. Research has shown that CSCs can initiate tumor development and play a significant role in tumor relapse and metastasis. Indeed, evidence is accumulating that treatments, such as chemotherapy and radiation, can increase the proliferation of CSCs. Investigations are underway into the molecular signaling pathways involved in tumor cell repopulation. The small subpopulation of CSCs in gastric cancer may be a rational treatment target.
