2013 Fiscal Year Final Research Report
Development of novel target therapy for soft tissue sarcoma stem cells
| 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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| 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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Research Products
(44 results)
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[Journal Article] Tailored therapeutic strategies for synovial sarcoma : Receptor tyrosine kinase pathway analyses predict sensitivity to the mTOR inhibitor RAD0012014
Author(s)
Yasui, H., Naka, N., Imura, Y., Outani, H., Kaneko, K., Hamada, KI., Sasagawa, S., Araki, N., Ueda, T., Itoh, K., Myoui, A., and Yoshikawa, H
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Journal Title
Cancer Lett
Volume: 347(1)
Pages: 114-122
DOI
Peer Reviewed
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[Journal Article] Dynamic analysis of lung metastasis by mouse osteosarcoma LM8-VEGF is a candidate for anti-metastasis therapy2013
Author(s)
Tanaka, T., Yui, Y., Naka, N., Wakamatsu, T., Yoshioka, K., Araki, N., Yoshikawa, H., and Itoh, K
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Journal Title
Clinical & Experimental Metastasis
Volume: 30
Pages: 369-379
DOI
Peer Reviewed
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[Journal Article] Changes in cell migration of mesenchymal cells during osteogenic differentiation2011
Author(s)
Ichida, M., Yui, Y., Yoshioka, K., Tanaka, T., Wakamatsu, T., Yoshikawa, H., Itoh, K
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Journal Title
FEBS Letters
Volume: 585
Pages: 4018-4024
DOI
Peer Reviewed
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[Journal Article] A Role for SNX1 in the Regulation of EGF-Dependent Phosphorylated EGFR Endocytosis Via the Early/Late Endocytic Pathway in a Gefitinib-Sensitive Human Lung Cancer Cells2011
Author(s)
Nishimura, Y., Yoshioka, K., Takiguchi, S., Bereczky, B., Nakabeppu, Y., and Itoh, K
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Journal Title
Current Signal Transduction Therapy
Volume: 6(3)
Pages: 383-395
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