Glucocorticoids are commonly used in clinic but are also a double-edged sword. While treating tumors, they are reported to promote tumor growth and metastasis. To explore the role and elucidate the mechanism of dexamethasone in promoting tumor growth and metastasis, we detected the levels of cortisol and adrenocorticotropic hormone (ACTH) in peripheral blood of patients with gastric cancer, and immunohistochemical staining was used to detect the expression of ROR1 in the surgically resected gastric cancer samples. The levels of cortisol and ACTH in peripheral blood of patients with stage III and IV gastric cancer were higher than those of patients with stage I/II gastric cancer. Dexamethasone up-regulated the ROR1 level on gastric cancer cell lines in a concentration-dependent manner. Gastric cancer specimen with high ROR1 had higher rates of relapse and metastasis than gastric adenocarcinomas expressing low levels of ROR1.Gastric cancer patients with high expression of ROR1 had a short survival time. ROR1 was expressed by gastric cancer cell lines, but not on normal gastric epithelial cell line. Suppressing ROR1 in gastric cancer cell lines impaired their invasion, migration, scratch healing and clone formation ability in vitro and slowed down the tumor growth of MKN-45 cells in immunodeficient mice in vivo. Collectively, our study indicated that dexamethasone up-regulated ROR1 levels on gastric cancer cells. ROR1 participated in and mediated the role of dexamethasone in promoting gastric tumor growth, and blocking ROR1 can prevent the tumor growth.
Keywords: Dexamethasone; Gastric cancer; Glucocorticoid; ROR1; Stress.
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