Deletion of Yin Yang 1 protein in osteosarcoma cells on cell invasion and CXCR4/angiogenesis and metastasis.
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.
de Nigris
Filomena
F
Department of General Pathology, Division of Clinical Pathology, 1st School of Medicine, II University of Naples, Naples, Italy.
Rossiello
Raffaele
R
Schiano
Concetta
C
Arra
Claudio
C
Williams-Ignarro
Sharon
S
Barbieri
Antonio
A
Lanza
Alessandro
A
Balestrieri
Antonio
A
Giuliano
Maria Teresa
MT
Ignarro
Louis J
LJ
Napoli
Claudio
C
D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000473:pathology; D012516:Osteosarcoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D050986:YY1 Transcription Factor / Q000172:deficiency* / Q000235:genetics
C527276:CXCR4 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D050986:YY1 Transcription Factor