Deletion of Yin Yang 1 Protein in Osteosarcoma Cells on Cell Invasion and CXCR4/Angiogenesis and Metastasis

Abstract

We know that the Yin Yang 1 protein (YY1) overexpression is positively and strongly correlated with the degree of malignancy of bone tumors. Therefore, we questioned whether we could influence cell invasiveness by deleting YY1 in human osteosarcoma cells (SaOs-2), as tested in Matrigel-coated filters and metastasis implantation of such osteosarcoma cells in vivo, by serial analysis with nuclear magnetic resonance. Moreover, we focused our work on the chemokine receptor CXCR4 and its inhibition by T22 antibody, as well as on systemic (direct in vivo assay) and computer-assisted imaging of angiogenesis-related metastasis. Results showed that cell invasiveness and metastasis implantation by wild-type SaOs-2 cells, as evaluated by histology and immunohistochemistry, are associated with up-regulation of CXCR4 expression, which in turn was significantly reduced by T22. In addition, deletion of YY1 (siRNAYY1-SaOs-2) induced a significant decrease of cell invasion and metastasis growth. This phenomenon was associated with decreased vascular endothelial growth factor (VEGF)/angiogenesis and a complex rearrangement of the gene expression profile as evaluated by microarray analysis. In conclusion, YY1 and VEGF/CXCR4 seem to intervene in the pathogenesis of the malignant phenotype of osteosarcoma by acting on cell invasiveness and metastasis growth. [Cancer Res 2008;68(6):1797-808]

Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor survival in soft‐tissue sarcoma

“…While, Kijowski et al 35 demonstrated the stimulation of VEGF secretion by SDF-1-CXCR4 axis, using human hematopoietic cell lines. Because then, a close correlation between CXCR4 and VEGF expression has been demonstrated in epithelial malignancies 12,13 and osteosarcoma, 36 both in vitro and in vivo. In our previous study, we found a significant positive correlation between immunohistochemical VEGF and CXCR4 expression.…”

CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia

“…The search site predicted a series of transcription factors that might be involved in the transcriptional regulation of let-7a (Table 1). The transcription factor Yin Yang 1 (YY1), ranked first in the prediction, is a member of the polycomb group and has been shown to be involved in CXCR4 signaling (25)(26)(27)(28)(29).…”

Orthopaedic Research in Italy: State of the Art

“…Genetic mutations and polymorphisms, which provide predisposition to the onset of osteosarcoma and affect survival, were also taken into account (25,26,27). Other genetic studies concern the mechanisms of resistance to cisplatin (28), doxorubicin and methotrexate (29).…”