Deletion of Yin Yang 1 protein in osteosarcoma cells on cell invasion and CXCR4/angiogenesis and metastasis

Filomena De Nigris, Raffaele Rossiello, Concetta Schiano, Claudio Arra, Sharon Williams-Ignarro, Antonio Barbieri, Alessandro Lanza, Antonio Balestrieri, Maria Teresa Giuliano, Louis J. Ignarro, Claudio Napoli

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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.

Original languageEnglish
Pages (from-to)1797-1808
Number of pages12
JournalCancer Research
Volume68
Issue number6
DOIs
Publication statusPublished - Mar 15 2008

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YY1 Transcription Factor
Osteosarcoma
Neoplasm Metastasis
Vascular Endothelial Growth Factor A
Chemokine Receptors
Microarray Analysis
Growth
Transcriptome
Neoplasms
Histology
Up-Regulation
Magnetic Resonance Spectroscopy
Immunohistochemistry
Phenotype
Bone and Bones

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Deletion of Yin Yang 1 protein in osteosarcoma cells on cell invasion and CXCR4/angiogenesis and metastasis. / De Nigris, Filomena; Rossiello, Raffaele; Schiano, Concetta; Arra, Claudio; Williams-Ignarro, Sharon; Barbieri, Antonio; Lanza, Alessandro; Balestrieri, Antonio; Giuliano, Maria Teresa; Ignarro, Louis J.; Napoli, Claudio.

In: Cancer Research, Vol. 68, No. 6, 15.03.2008, p. 1797-1808.

Research output: Contribution to journalArticle

De Nigris, F, Rossiello, R, Schiano, C, Arra, C, Williams-Ignarro, S, Barbieri, A, Lanza, A, Balestrieri, A, Giuliano, MT, Ignarro, LJ & Napoli, C 2008, 'Deletion of Yin Yang 1 protein in osteosarcoma cells on cell invasion and CXCR4/angiogenesis and metastasis', Cancer Research, vol. 68, no. 6, pp. 1797-1808. https://doi.org/10.1158/0008-5472.CAN-07-5582
De Nigris, Filomena ; Rossiello, Raffaele ; Schiano, Concetta ; Arra, Claudio ; Williams-Ignarro, Sharon ; Barbieri, Antonio ; Lanza, Alessandro ; Balestrieri, Antonio ; Giuliano, Maria Teresa ; Ignarro, Louis J. ; Napoli, Claudio. / Deletion of Yin Yang 1 protein in osteosarcoma cells on cell invasion and CXCR4/angiogenesis and metastasis. In: Cancer Research. 2008 ; Vol. 68, No. 6. pp. 1797-1808.
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