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.

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