Small interfering RNA-directed knockdown of S100A4 decreases proliferation and invasiveness of osteosarcoma cells

Cancer Lett. 2010 Dec 28;299(2):171-81. doi: 10.1016/j.canlet.2010.08.016. Epub 2010 Sep 19.

Abstract

Osteosarcoma is the most common osteogenic malignant tumor characterized by a high level of malignancy, relapse, metastasis and poor prognosis. S100A4 has been implicated in the proliferation, cell cycle progression, and metastasis of many malignant tumors, although the roles of S100A4 in osteosarcoma have not been documented. This study showed that the expression of S100A4 was found in two osteosarcoma cell lines MG-63 and U-2OS, and in 70.7% of osteosarcoma clinical tissues, and the expression was correlated with the expression of CD44V6. In addition, transfection with S100A4 siRNA significantly reduced the proliferation and the invasiveness of MG-63 cells. Furthermore, S100A4 siRNA down-regulated the expression of CD44 and MMP2, suggesting that S100A4 may promote the proliferation, invasion and metastasis of osteosarcoma cells by regulating the expression of other proteins that are crucial in modulating cell-ECM adhesion and facilitating ECM degradation. Therefore, siRNA-directed knockdown of S100A4 may represent a viable clinical therapy for osteosarcoma.

MeSH terms

  • Adult
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Neoplasm Invasiveness
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • RNA Interference*
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / genetics*
  • S100 Proteins / metabolism
  • Transfection
  • Young Adult

Substances

  • CD44v6 antigen
  • Hyaluronan Receptors
  • RNA, Small Interfering
  • S100 Calcium-Binding Protein A4
  • S100 Proteins
  • S100A4 protein, human
  • Matrix Metalloproteinase 2