Mesenchymal stem cell-derived CCN2 promotes the proliferation, migration and invasion of human tongue squamous cell carcinoma cells

Cancer Sci. 2017 May;108(5):897-909. doi: 10.1111/cas.13202. Epub 2017 Apr 26.

Abstract

Recent studies have demonstrated that mesenchymal stem cells (MSC) exhibit a tropism to tumors and form the tumor stroma. In addition, we found that MSC can secrete different types of factors. However, the involvement of MSC-derived factors in human tongue squamous cell carcinoma (TSCC) growth has not been clearly addressed. The CCN family includes multifunctional signaling molecules that affect the initiation and development events of various tumors. In our study, we report that CCN2/connective tissue growth factor (CTGF) was the most highly induced among the CCN family members in MSC that were co-cultured with TSCC cells. To evaluate the relationship between CCN2 and TSCC growth, we downregulated MSC-derived CCN2 expression with shRNA targeting CCN2 and found that MSC-secreted CCN2 promotes TSCC cell proliferation, migration and invasion. We also confirmed that MSC-derived CCN2 partially accelerated tumor growth in vitro. Taken together, these results suggest that MSC-derived CCN2 contributes to the promotion of proliferation, migration and invasion of TSCC cells and may be a possible therapy target in the future.

Keywords: CCN2; mesenchymal stem cells; migration; proliferation; tongue squamous cell carcinoma.

MeSH terms

  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Connective Tissue Growth Factor / genetics*
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / pathology

Substances

  • CCN2 protein, human
  • Connective Tissue Growth Factor