Hypoxia and CD11b+ Cell Influx Are Strongly Associated With Lymph Node Metastasis of Oral Cancer

Anticancer Res. 2020 Dec;40(12):6845-6852. doi: 10.21873/anticanres.14706.

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.

Keywords: CD11b+ cell; LN metastasis; Oral cancer; hypoxia; lymphangiogenesis.

MeSH terms

  • Animals
  • CD11b Antigen / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Disease Models, Animal
  • Fluorescent Antibody Technique
  • Humans
  • Hypoxia / metabolism*
  • Lymphangiogenesis
  • Lymphatic Metastasis
  • Lymphocytes / metabolism*
  • Lymphocytes / pathology
  • Mice
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology*
  • Mouth Neoplasms / surgery
  • Neoplasm Staging
  • Neovascularization, Pathologic / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • CD11b Antigen
  • ITGAM protein, human