RON Is Associated with Tumor Progression in Head and Neck Squamous Cell Cancer

Abstract

Objective: To investigate that the recepteur d’origine nantais (RON) expression is expressed in human head and neck squamous cell cancer (HNSCC) cells and to evaluate whether RON affects tumor cell behavior in head and neck cancer cell lines, thus serving as a target for molecular therapy in a preclinical model. Method: The protein expression of RON by immunohistochemistry and western blot analysis was investigated in human head-neck cancer tissues. To evaluate the impact of RON knock down on behavior of human head-neck cancer cell lines, invasion and migration assays using small-interfering RNA were performed. Western blot analysis was used to assess alteration in protein expression. Results: RON positive immunoreactions were observed relative to adjacent mucosal tissue in all 28 cases, while 15 cases (53.6%) were over-expressed. RON over-expression was significantly associated with lymph node metastasis. RON protein expression was increased in cervical metastatic lymph node tissue by western blot analysis. Treatment of RON ligand, macrophage stimulating proetin (MSP) increased cell migration and invasion in human head-neck cancer cell lines (SNU 1041, PCI 50). The knockdown of RON significantly suppressed tumor cell migration, invasion. The Erk, p38 phosphorylation was reduced by knockdown of RON in PCI 50. Conclusion: RON expression might play an important role in the progression, especially lymphatic metastasis of head and neck squamous cell cancer. Further investigations are needed to assess the potential of RON-directed molecular therapy in head and neck squamous cell cancer.