2002 Fiscal Year Final Research Report Summary
Molecular insight of cancer metastasis of gastrointestinal tract -strategies of therapeutic implication
| Project/Area Number |
12470254
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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 |
Digestive surgery
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| Research Institution | Kanazawa University |
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Principal Investigator |
MAI Masayoshi Kanazawa University, Cancer Research Institute, Professor, がん研究所, 教授 (80092807)
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| Co-Investigator(Kenkyū-buntansha) |
YASUMOTO Kazuo Kanazawa University, Cancer Research Institute, Assistant Professor, がん研究所, 助手 (90262592)
MINAMOTO Toshinari Kanazawa University, Cancer Research Institute, Professor, がん研究所, 教授 (50239323)
TAKAHASHI Yutaka Kanazawa University, Cancer Research Institute, Associate Professor, がん研究所, 助教授 (10179541)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Matrix metalloproteinase / angiogensis / β-catenin / Cancer oteinases metastasis / Angiogenic inhibitor / liver metastasis |
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| Research Abstract |
Metastasis is the most threatening event for cancer patients. In considering the main steps in the process of tumor invasion and metastases, the mechanism for invasion of the tumor cells through tissue barriers of the extracellular matrix(ECM) and neovascularization are not well understood, but they appeared to modulate the stromal microenvromental events in the cancer host.
To clarify molecular mechanism of cancer metastasis, especially matrix metalloproteinase and angiogenesis using clinical materials, and to inhibit metastasis. We already reported that MT1-MMP expressed in the cancer cell membrane modulates and induces active MMP-2 existed in cancer stroma such as fibroblast or macrophages resulting in degradation of ECM in the process of cancer invasion and metastasis. We also reported that enhanced production of MMP-7 is implicated in the metastasis prognosis of human gastric and colorectal cancer. On the other hand, angiogenesis is essential for tumor growth and metastasis and dep
… More
ends on production of angiogenic factors by tumor sells and/or infiltrating cells. We hypothesied that tumors with hig expression of both VEGF and PD-ECGF, TGF-alpha in cancer stroma might produce higher vessels counts. Our results on PD-ECGF and VEGF may be additive or syneigistic in their action, leading to the highest vessel count and metastasis. From the clinical viewpoint we reported clinical significance of these angiogenic factors in various cancer. In order to know metastatic potential before surgery he also investigated mRNA(ISH) analysis of these metastasis related gene products such as MMP-2, VEGF, E-Cadherin, using gastric biopsy specimens. Recently we have obtained a result suggesting that affects different patterns of β-catenin activation in the tumors. Our observation that is more important than the molecular mechanisms underlying the difference in activation patterns was that oncogenic β-catenin activation in the tumor invasion front is an independent and reliable indicator of membership in a subset of colon cancer patients who are highly susceptible to tumor recurrence and have a less favorable survival rate. Recent advances of cancer biology has brought us new ideas for cytostatic therapeutic targets such as MMPs, Adhesion molecules, signal transduction pathway and angiogensis. We reported that DMFO(Polyamine inhibitor) induces apoptosis as well as anti-angiogenesis in the inhibition of tumor growth and metastasis in human gastric cancer models. The hope is that by use of selective inhibitors for these targets such as MMPs and angiogenic factors we can achieve a halt in tumor progression without significant toxicity. Less
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[Publications] Fujimoto, T., Zhang, B., Minami, S., Wang, X., Takahashi, Y., Mai, M.: "Evaluation of intraoperative intrape itoneal cytology for advanced gastric carcinoma."Oncology. 62. 201-208 (2002)
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