Gastric cancer is the fourth most common cancer worldwide,with a high rate of death and low5-year survival rate.To date,there is a lack of efficient therapeutic protocols for gastric cancer.Recent studies suggest that cancer stem cells(CSCs)are responsible for tumor initiation,invasion,metastasis,and resistance to anticancer therapies.The CSCs have been shown to migrate from tumor tissues into blood vessels to travel to distant sites in body to conduct metastatic activity.In circulation,there are existed several stresses to kill the cells.Therefore,first of all,the CSCs must try to survive when they enter and stay in the circulating bloodstreams in body.However,little is known how metastatic CSCs are survival in bloodstream.Here,weidentify CSCs in tumor tissues in stomach and peripheral blood from patients withgastric adenocarcinoma.CSCs of human GAC(GCSCs)that are isolated from tumortissues and peripheral blood of patients carried CD44and CD54surface markers,generated tumors that highly resemble the original human tumors when injectedinto immunodeficient mice,differentiated intogastricepithelialcellsin vitro,andself-renewed in vivo and in vitro.The gene expression profiles and single cell assaysin vivo and in vitro were performed and identified that PDGF receptor alpha(PDGFRA)was exclusively expressed in the CSCs directly derived from the periphery bloodsamples of human patients with gastric adenocarcinoma and was activated byautocrine and platelet secreting PDGF.The PDGFRA activation maintained thesurvival of the CSCs by preventing autophagy via AKT pathway.The data provide anew inside mechanism how the circulating CSCs survive and suggest a target torestrain the survival of gastric CSCs in bloodstreams to prevent metastasis andrestrict the CSC homing to the stomach after surgically,radiotherapeutically,orchemotherapeuticallyremovability of tumor masses in human patients with gastricadenocarcinoma.