COBRE: NDSU: PROJECT 3: MMP-9 IN APOPTOSIS OF PROSTATE CANCEL CELLS

COBRE：NDSU：项目 3：MMP-9 在前列腺癌细胞凋亡中的作用

• 批准号: 8167863
• 负责人: BIN GUO
• 金额: $ 7.09万
• 依托单位: NORTH DAKOTA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167863
• 关键词: Apoptosis; Apoptotic; Basement membrane; Cell Survival; Cells; Centers of Research Excellence; Cleaved cell; Clinical Trials; Collagen; Computer Retrieval of Information on Scientific Projects Database; Funding; Future; Gelatinase B; Grant; Inhibition of Matrix Metalloproteinases Pathway; Institution; Malignant - descriptor; Malignant neoplasm of prostate; Mammals; Matrix Metalloproteinase Inhibitor; Matrix Metalloproteinases; Mediating; Neoplasm Metastasis; Patients; Prostate; Protein Isoforms; Regulation; Research; Research Personnel; Resources; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Source; Staging; Treatment Efficacy; United States National Institutes of Health; cancer cell; cancer therapy; cytokine; inhibitor/antagonist; neoplastic cell; receptor; tumor progression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Matrix metalloproteinases (MMPs) are promising targets for cancer therapy. However, recent clinical trials of MMP inhibitors have been disappointing. Certain MMPs may regulate apoptosis signaling pathways and sensitize tumor cells to apoptotic signals. Inhibition of these MMPs will promote tumor cell survival and this effect may offset the beneficial activity in inhibition of metastasis. Matrix metalloproteinase-9 (MMP-9) expression is significantly increased in malignant prostate cancers. In addition to its ability to cleave collagens and basement membrane components, MMP-9 also cleaves and activates the multifunctional cytokine TGF-¿. TGF-¿ (having three isoforms in mammals: TGF-¿1, ¿2, ¿3) is an important regulator of normal and malignant prostate. While TGF-¿1 induces apoptosis in certain prostate cancer cells, TGF-¿2 blocks apoptosis. By activating all three isoforms of TGF-¿, MMP-9 may have different net effect on prostate cancer apoptosis depending on the status of expression of TGF-¿ isoforms, their receptors, and the downstream signaling molecules. There is a critical need to determine the effects of MMP-9 on apoptosis in prostate cancer. Presumable, inhibition of MMP-9 will be beneficial in patients where MMP-9-mediated TGF-¿ activation has an anti-apoptotic effect in cancer cells. Selection of appropriate patients according to the status of TGF-¿ signaling machinery may be critical for future clinical trials to evaluate the therapeutic efficacy of MMP-9 inhibitors. The objective of this research is to define the role of MMP-9 in prostate cancer apoptosis and how the effects of MMP-9 on apoptosis change along with prostate cancer progression. At the completion of this project, we expect to clarify the role of MMP-9 in apoptosis regulation in prostate cancer and how this role may change in relation with the changes of TGF-¿ signaling at different stages of prostate cancer progression.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 基质金属蛋白酶(MMPs)是肿瘤治疗的重要靶点。然而，最近 基质金属蛋白酶抑制剂的临床试验一直令人失望。某些MMPs可能调节细胞凋亡 信号通路和使肿瘤细胞对凋亡信号敏感。抑制这些MMPs将会 促进肿瘤细胞存活，这种作用可能抵消了抑制肿瘤细胞存活的有益活性 转移。基质金属蛋白酶-9(MMP9)表达显著增加 恶性前列腺癌。除了能够裂解胶原蛋白和基底膜 膜成分，基质金属蛋白酶-9也裂解和激活多功能细胞因子 转化生长因子-β。 转化生长因子β(在哺乳动物中有三种异构体：转化生长因子β1、转化生长因子β2、转化生长因子β3)是一种重要的调节因子。 正常的和恶性的前列腺。而转化生长因子-β1诱导某些前列腺癌的细胞凋亡 细胞，转化生长因子β2阻断细胞凋亡。通过激活所有三种转化生长因子-β亚型，基质金属蛋白酶-9可能 对前列腺癌细胞凋亡的净作用取决于转化生长因子-β亚型、其受体和下游信号分子的表达状况。有一个关键的问题 需要确定基质金属蛋白酶-9在前列腺癌细胞凋亡中的作用。可以想见， 抑制基质金属蛋白酶-9将有益于基质金属蛋白酶-9介导的转化生长因子-β活化的患者 癌细胞中的一种抗凋亡作用。 根据转化生长因子-β信号机制的状态选择合适的患者可能是 这对于未来的临床试验评估基质金属蛋白酶-9抑制剂的疗效至关重要。这个 本研究的目的是明确基质金属蛋白酶-9在前列腺癌细胞凋亡中的作用以及如何 基质金属蛋白酶-9在细胞凋亡中的作用随前列腺癌进展而变化。在 这个项目的完成，我们希望澄清基质金属蛋白酶-9在细胞凋亡调控中的作用。 前列腺癌及其与转化生长因子信号转导的关系 在前列腺癌进展的不同阶段。