Inhibition of CDC42 reduces macrophage recruitment and suppresses lung tumorigenesis in vivo

J Recept Signal Transduct Res. 2021 Oct;41(5):504-510. doi: 10.1080/10799893.2020.1828916. Epub 2020 Oct 1.

Abstract

Background: Cell division control (CDC) 42 has been involved in the regulation of diverse cancers. Macrophage recruitment plays an important role in the pathogenesis and development of tumor. However, it remains unclear whether CDC42 contributes to macrophage recruitment and lung tumorigenesis in vivo.

Methods: Small interference RNA (siRNA) was used to knock down CDC42 in the Lewis lung carcinoma (LLC)1. The invasion capability of CDC42 knockdown LLC1 cells was evaluated. LLC1 cells with CDC42 targeted small hairpin RNA (shRNA) were inoculated into C57BL/6 mice to establish the tumor-bearing animal model Tumor size and metastasis related proteins were measured. In addition, the invasion of macrophages in the tumor site as well as macrophage chemokine were also determined in the model.

Results: The capacity of invasion and metastasis of LLC1 cells significantly decreased when CDC42 was knocked down. When inoculated with CDC42 knockdown LLC1 cells in vivo, the tumor size and metastasis related proteins levels both decreased. The invasion capacity of macrophages and the associated macrophage chemokine were also significantly down-regulated.

Conclusion: Our data suggest that the inhibition of CDC42 expression in lung cancer cells can significantly prevent the pathogenesis and development of tumor in an allograft tumor model in vivo, which might provide a novel therapeutic target and potential strategy for lung cancer treatment in the future.

Keywords: CDC42 knockdown; Small interference RNA (siRNA); allograft tumor; lung tumorigenesis; macrophage invasion.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis / immunology
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology*
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / metabolism
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Lewis Lung / prevention & control*
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal*
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering / genetics*
  • cdc42 GTP-Binding Protein / antagonists & inhibitors*
  • cdc42 GTP-Binding Protein / genetics

Substances

  • RNA, Small Interfering
  • CDC42 protein, human
  • cdc42 GTP-Binding Protein