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

COBRE：NDSU：项目 3：MMP-9 在前列腺癌细胞凋亡中的作用

• 批准号: 7959603
• 负责人: BIN GUO
• 金额: $ 13.76万
• 依托单位: NORTH DAKOTA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959603
• 关键词: Apoptosis; Apoptotic; Basement membrane; Cell Survival; Centers of Research Excellence; Cleaved cell; Clinical Trials; Collagen; Computer Retrieval of Information on Scientific Projects Database; Disease; 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; Peptide Hydrolases; 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 中心，不一定是研究者的机构。 基质金属蛋白酶 (MMP) 是癌症治疗的有希望的靶标。 MMP 抑制剂的临床试验令人失望。某些 MMP 可能调节细胞凋亡。 抑制这些 MMP 会增强信号通路并使肿瘤细胞对凋亡信号敏感。 促进肿瘤细胞存活，这种作用可能会抵消抑制肿瘤细胞的有益活性。 基质金属蛋白酶-9 (MMP-9) 表达显着增加。 除了其切割胶原蛋白和基底的能力之外。 MMP-9 还可以裂解和激活多功能细胞因子 转化生长因子-¿ 。 转化生长因子-¿ （在哺乳动物中具有三种同工型：TGF-¿1、¿2、¿3）是重要的调节因子 正常和恶性前列腺。 1 诱导某些前列腺癌的细胞凋亡 细胞，TGF-¿ 2 通过激活 TGF-¿ 的所有三种亚型来阻断细胞凋亡。 , MMP-9 可能有 根据 TGF-¿ 的表达状态，对前列腺癌细胞凋亡的净效应不同同种型、它们的受体和下游信号分子。 需要确定 MMP-9 对前列腺癌细胞凋亡的影响。 抑制 MMP-9 将有益于 MMP-9 介导的 TGF-¿激活有 对癌细胞具有抗凋亡作用。 根据TGF-¿的状态选择合适的患者信号机制可能是 对于未来评估 MMP-9 抑制剂治疗效果的临床试验至关重要。 本研究的目的是确定 MMP-9 在前列腺癌细胞凋亡中的作用以及如何 MMP-9 对细胞凋亡的影响随着前列腺癌的进展而变化。 该项目完成后，我们期望阐明MMP-9在细胞凋亡调节中的作用 前列腺癌以及这种作用如何随着 TGF-¿ 的变化而变化信令 在前列腺癌进展的不同阶段。