TY - JOUR ID - 25840 TI - Knockdown of S100A4 Decreases Tumorigenesis and Metastasis in Osteosarcoma Cells by Repression of Matrix Metalloproteinase-9 JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 Y1 - 2011 PY - 2011 VL - 12 IS - 8 SP - 2075 EP - 2080 KW - osteosarcoma KW - Metastasis KW - S100A4 KW - MMP-9 expression KW - Cell migration DO - N2 - Osteosarcoma (OS), the most frequent bone tumor in children and adolescents, is highly malignant. Metastases are the major cause of death, and patients with relapse have a poor prognosis. Given the associations of S100A4 with OS and tumor metastasis, we explored its potential roles in OS metastasis. Among 32 OS (16 metastatic and 16 non- metastatic) specimens examined, we found a significant increase of S100A4 mRNA in metastatic tissues, and more importantly, expression of S100A4 and MMP-9 to be strongly correlated in patients who had lymph node or distant metastasis. We observed that siRNA mediated suppression of the S100A4 gene significantly reduced the proliferative and invasive capability of highly invasive OS cells, with a reduced rate of tumor growth and metastasis under in vivo conditions. Matrix metalloproteinase 9 (MMP-9) proved highly responsive to S100A4 gene suppression, demonstrating significant reduction in proteolytic activity, while overexpression of S100A4 increased the expression and proteolytic activity of MMP-9. Links of S100A4 with cell motility were confirmed by depletion which resulted in reduced cell migration. Moreover, loss of cell metastatic potential was completely rescued by overexpression of MMP-9. Collectively, our findings indicate that S100A4 contributes to OS metastasis by stimulating MMP-9 expression, suggesting potential as a novel diagnostic biomarker for OS progression as well as a therapeutic target. UR - https://journal.waocp.org/article_25840.html L1 - https://journal.waocp.org/article_25840_cf86e2c170bbe5743df8747547aa7294.pdf ER -