Cancer‑associated fibroblast‑derived exosomal miR‑382‑5p promotes the migration and invasion of oral squamous cell carcinoma

Oncol Rep. 2019 Oct;42(4):1319-1328. doi: 10.3892/or.2019.7255. Epub 2019 Jul 30.

Abstract

Oral squamous cell carcinoma (OSCC), with high potential for metastasis, is the most common malignant tumor of the head and neck. Cancer‑associated fibroblasts (CAFs) are the main stromal cells in the microenvironment and aggravate tumor progression. However, whether CAFs are associated with the progression of OSCC remains unknown and the underlying mechanism remains unclear. In the present study, the role of CAFs in mediating OSCC cell migration and invasion was investigated, and the participation of exosomal miR‑382‑5p in this process was elucidated. In this study, according to the α‑SMA staining with immunohistochemistry, 47 OSCC patients were divided into CAFs‑rich and CAFs poor groups, and association of CAF density and clinicopathologic features of the OSCC patients were analyzed with Pearson χ2 test. Transwell assay was used for evaluating cell migration and invasion ability of OSCC cells after being co‑cultured with NFs or CAFs, or after added exosomes. qPCR was used to detect the expression of miR‑382‑5p. Western blot analysis was used to measure the expression of migration and invasion‑associated proteins. In the present study, the CAF density in tumor tissues was found to be relevant to OSCC lymph node metastasis and TNM stage. Furthermore, we revealed that miR‑382‑5p was overexpressed in CAFs compared with that in fibroblasts of adjacent normal tissue and miR‑382‑5p overexpression was responsible for OSCC cell migration and invasion. Finally, we demonstrated that CAF‑derived exosomes transported miR‑382‑5p to OSCC cells. The present study confirmed a new mechanism of CAF‑facilitated OSCC progression and may be beneficial for identifying new cancer therapeutic targets.

MeSH terms

  • Actins / biosynthesis
  • Adult
  • Aged
  • Cancer-Associated Fibroblasts / metabolism
  • Cancer-Associated Fibroblasts / pathology*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Exosomes / genetics*
  • Exosomes / metabolism
  • Exosomes / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasm Metastasis
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / pathology*

Substances

  • ACTA2 protein, human
  • Actins
  • MIRN382 microRNA, human
  • MicroRNAs