| Project/Area Number |
18591650
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses |
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Principal Investigator |
YOSHIOKA Kiyoko Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses, Osaka Medical Center for Cancer and Cardiovascular Diseases, Biology, Chief Investigator (40342993)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Kazuyuki Osaka Medical Center for Cancer and Cardiovascular Diseases, Biology, Department Head (20301806)
YOSHIKAWA Hideki Osaka University Graduate School of Medicine, Department of Orthopaedics, Professor (60191558)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | SSX / osteosarcoma / tumor formation / lung metastasis / NASBA / colony formation / invasion / siRNA |
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| Research Abstract |
The SSX genes were initially identified as fusion partners to the SS18 gene in human synovial sarcoma carrying a recurrent t(X ; 18)(p11.2 ; q11.2) chromosomal translocation. Using Nucleic Acid Sequence-Based Amplification, we found that the level of expression positively correlated with clinical stage, especially the metastatic case present very high SSX expression. We made stable transfectants with wild type SSX using human osteosarcoma cell line, Saos-2, and human fibrosarcoma cell line, HT1080. The SSX transfectants promoted colony formation in soft agar and tumor formation in nude mice. The transfectants also increased motility and invasiveness using Boyden chamber assay. Using oligomicroarray, we found several changes in gene expression profile. Overexpression of SSX increased the expression of MMP1, and the transfectants showed enhances MMP1 activity. By contrast, the lowering of the endogenous expression of SSX in HT1080 cells and Saos-2 cells by the treatment with sequence specific siRNA markedly decreased chemotaxis, invasiveness and cellular proliferation in 3D collagen gel. We also evaluated the efficacy of siRNA in vivo using HT1080 cell xenograft model.
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