Hypoxia and CD11b+ cell influx are strongly associated with lymph node metastasis of oral cancer

Abstract

Background/Aim: Treatment failure in oral cancer is mainly caused by uncontrolled cervical lymph node (LN) metastasis. We previously reported that CD11b+ cells are recruited into tumor hypoxic areas following radiation, leading to re-vascularization and relapse. Since lymphatic vessel formation has similarities with vascular formation, we examined whether surgery induces hypoxia and stimulates lymphangiogenesis. Materials and Methods: The recruitment of CD11b+ cells and the formation of lymphatic vessels were examined using orthotopic tongue cancer mouse models with glossectomy. Results: Surgery on OSC-19 tumor induced LN metastases and hypoxia, followed by CD11b+ cell influx. These phenomena were not observed in the no tumor or SAT tumor models. Stimulation of lymphangiogenesis was observed in the CD11b+ cell influx area, as the tumor grew. The localization of CD11b+ cells was changed from the lymph nodules to the medullary sinuses. Conclusion: Surgery-induced hypoxia in oral tumors leads to CD11b+ cell infiltration, lymphangiogenesis, and LN metastasis.