| Project/Area Number |
23390372
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
ITOH Kazuyuki 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), 研究所, 部門長 (20301806)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIOKA Kiyoko 地方独立行政法人大阪府立病院機構, 大阪府立成人病センター(研究所), 研究員 (40342993)
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| Co-Investigator(Renkei-kenkyūsha) |
YOSHIKAWA Hideki 大阪大学, 医学系研究科, 教授 (60191558)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2011: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 骨軟部腫瘍 / 分子標的治療 / 転移 / 幹細胞 |
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| Research Abstract |
VEGF-targeting anti-angiogenic therapy has been approved for soft-tissue sarcoma, including synovial sarcoma (SS); however, the mechanism underlying VEGF signal for sarcomagenesis in SS is unclear. Here, we show that SS fusion gene :SS18-SSX directs the VEGF signal outcome to cellular growth from differentiation. SS cells secrete large amounts of VEGF under spheroid culture conditions in autocrine fashion. SS18-SSX knockdown altered the VEGF signaling outcome, from proliferation to tubular differentiation, without affecting VEGF secretion, suggesting that VEGF signaling promoted cell growth in the presence of SS18-SSX. Thus, VEGF inhibitors blocked both host angiogenesis and spheroid growth. Simultaneous treatment with VEGF and CXCL12/CXCR4 inhibitors and/or ifosfamide effectively suppressed tumor growth both in vitro and in vivo. SS18-SSX directs the VEGF signal outcome from endothelial differentiation to spheroid growth, and VEGF and CXCR4 are critical therapeutic targets for SS.
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