Gastric cancer (GC) is one of the deadliest cancers in the world. With its lacking of early diagnostic methods, metastasis and recurrence lead to a low 5-yeard survival rate. Discovering mechanisms of gastric cancer and thus developing new strategies for gastric cancer diagnosis and therapy is urgent for clinicians and scientists. OSM receptor (OSMR) is a member of the interleukin 6 (IL-6) receptor family and transduces signaling events induced by its major ligand OSM. Interaction between OSMR and OSM plays key roles in inflammation, hematopoiesis, and development, and is increasingly being recognized as an important contributor to cancer progression. However, the role of OSM-OSMR interaction on GC is still not known.
Expression of OSM receptor (OSMR) was performed by RT-PCR, immunohistochemistry and Western Blot in gastric cancer tissues and cell lines. The malignant effects of OSM-OSMR interaction on gastric cancer cells in vitro and in vivo were examined.
OSMR is highly expressed in GC tissues and cell lines, and OSMR levels are positively associated with age, T stage, tumor size, lymph node metastasis, TNM stage, Lauren Classification and poor prognosis. In GC cells that overexpress OSMR, recombinant human OSM (rhOSM) treatment promotes cell proliferation, migration, invasion, EMT in virto, as well as tumorigenesis and peritoneal metastasis in vivo. These multiple pro-malignant effects induced by OSM-OSMR interaction are mediated by activation of STAT3/FAK/Src signaling pathway. Specific inhibition of OSM-OSMR interaction by silencing OSMR expression significantly inhibits STAT3/FAK/Src activation, leading to reduced cell proliferation, migration, invasion and EMT.
OSM-OSMR interaction contributes to the progression of GC through the activation of t STAT3/FAK/Src signaling pathway and OSMR could be a potential target for gastric cancer treatment.
Clinical trial identification
Legal entity responsible for the study
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine.
This study was supported by grants from National Natural Science Foundation of China (No.81272749, No.81572798 and No.91529302), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20152505).
All authors have declared no conflicts of interest.