Gr-1+CD11b+ cells facilitate Lewis lung cancer recurrence by enhancing neovasculature after local irradiation

Sci Rep. 2014 Apr 29:4:4833. doi: 10.1038/srep04833.

Abstract

Studies have shown that bone marrow-derived cells play an important role in tumor recurrence after chemotherapy and radiotherapy. In this study, we examined the relationship between the accumulation of Gr-1+CD11b+ cells and tumor recurrence after irradiation in tumor-bearing mice. By transplanting bone marrow cells into whole body-irradiated mice depleted of bone marrow, we assessed the role of Gr-1+CD11b+ cells in lung carcinoma models after local irradiation (LI). 20 Gy local irradiation could recruit CD11b+CXCR4+ cells into the irradiated tissues, and the recruited CD11b+CXCR4+ cells could promote tumor recurrence. Further 6 Gy whole body irradiation (WBI6Gy) could decrease tumor recurrence by inhibiting the accumulation of Gr-1+CD11b+ cells and then suppressing tumor vasculogenesis and angiogenesis. Our results suggest that the accumulation of CD11b+Gr-1+ cells promote tumor re-growth after local irradiation by enhancing tumor neovascularization, and low dose of whole body irradiation or irradiation of enlarged spleen may provide a new alternative for anti-angiogenesis therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11b Antigen / metabolism*
  • Carcinoma, Lewis Lung / metabolism*
  • Carcinoma, Lewis Lung / pathology*
  • Carcinoma, Lewis Lung / radiotherapy
  • Cell Movement
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / radiotherapy
  • Male
  • Mice
  • Myeloid Cells / metabolism
  • Myeloid Cells / radiation effects
  • Neoplasm Recurrence, Local
  • Neovascularization, Pathologic*
  • Nitric Oxide Synthase Type II / metabolism
  • Receptors, CXCR4 / metabolism
  • Receptors, Chemokine / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • CD11b Antigen
  • Gr-1 protein, mouse
  • Receptors, CXCR4
  • Receptors, Chemokine
  • Nitric Oxide Synthase Type II