Stress Related Hormone Results In The Phenotype Of Gastric Cancer Stem Cell By Breaking The Homostasis Between CD44 And MiRNA 373

Cancer stem cells (CSCs) have been defined as a unique subpopulation in tumors that possess the ability to initiate tumor growth and sustain tumor self-renewal. Although complicated and controversial, the stem cell as the progenitor of cancer has found support in leukemia research, and subsequently in some solid tumors. Takaishi have identified gastric cancer-initiating cells from a panel of human gastric cancer cell lines using cell surface marker CD44. The CD44(+) gastric cancer cells showed the stem cell properties of selfrenewal and the ability to form differentiated progeny and gave rise to CD44(-) cells.Objective Firstly, we identify gastric cancer-initiating cells from a primary gastric cancer and metastatic gastric cancer using cell surface marker CD44. Secondly, we focused on stress related hormone results in the phenotype of gastric cancer stem cell by breaking the homostasis between CD44 and miRNA 373.Methods All cell culture media were supplemented with 10% fetal bovine serum (FBS),10 mM HEPES, and 1% of penicillin-streptomycin, For surface marker analysis by flow cytometry,70%-90% confluent cells in a 100-mm cell plate were washed once with phosphate-buffered saline, and then cells were dissociated from plates using Trypsin-EDTA. Western blot method was used to detect CD44, Lin28 in primary and metastatic cancer. PCR was used to amplify the DNA target such as miR373, Rex-1 and Nanog. STAT3 and AP-1 were measured by double luciferase assay kit.Result The ratio of CD44(+) in metastatic gastric cancer is thirtyfold higher than that in primary cancer. Remarkable elevation of CD44 expression level and notable decrease of miRNA 373 expression level in metastasis focus compared with primary gastric tumor. Stress hormone can inhibit the expression of miRNA 373 and enhance the expression level of CD44 in gastric cancer cell line. Stress hormone can causes the phenotype of gastric cancer stem cell by breaking the homostasis between CD44 and miRNA 373 in animal model.Conclusion The ratio of CD44(+) in metastatic gastric cancer is higher than that in primary cancer. The difference is account for the recurrence and metastasis in gastric cancer. When stress related hormone broke the homostasis between CD44 and miRNA 373, the phenotype of gastric cancer stem cell may changed and tended to obtain invasive potential. This understanding provides a basis for promising new therapies which may specifically target gastrointestinal cancer stem cells.