2/2 Pilot Project 2: Langston University-UNTHSC Partnership for Cancer Research and Education

2/2 试点项目 2：兰斯顿大学-UNTHSC 癌症研究和教育合作伙伴关系

• 批准号: 10005235
• 负责人: PankaJ Chaudhary
• 金额: $ 6.14万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005235
• 关键词: Alteplase; Annexins; Binding Proteins; Biological Models; Blood; Bone Marrow; Bone Resorption; Bone Tissue; Calcium; Cancer Patient; Cell Adhesion Molecules; Cell surface; Cell-Cell Adhesion; Chromosome 10; Cleaved cell; Collaborations; Communities; Complex; Development; Disease; Endocytosis; Environment; Event; Exocytosis; Extracellular Matrix; Faculty; Fibrinolysis; Genes; Goals; Health Sciences; Hematopoietic stem cells; Homing; Human; Institutes; Ion Channel; Link; Malignant Neoplasms; Malignant neoplasm of prostate; Marrow; Mediating; Membrane; Metastatic Neoplasm to the Bone; Metastatic Prostate Cancer; Methods; Minority-Serving Institution; Molecular; Morbidity - disease rate; Mutate; Mutation; Neoplasm Circulating Cells; Neoplasm Metastasis; PTEN gene; Phospholipids; Phosphorylation; Pilot Projects; Plasmin; Plasminogen; Play; Process; Prostate Adenocarcinoma; Prostatic Neoplasms; Proteins; Reporting; Research; Research Personnel; Resistance development; Role; Signal Transduction; Stream; Survival Rate; Testing; Texas; Translating; Treatment Protocols; Tumor Suppressor Genes; Universities; Urokinase; Work; advanced prostate cancer; anticancer research; base; bone; cancer cell; cancer education; career; cell motility; driving force; effective therapy; epithelial to mesenchymal transition; experience; malignant phenotype; mortality; mouse model; neoplastic cell; new therapeutic target; osteoclastogenesis; osteogenic; overexpression; plasminogen receptor; precursor cell; prevent; prostate cancer cell; prostate cancer cell line; prostate cancer metastasis; prostate cancer model; prostate cancer progression; racial and ethnic; receptor; targeted agent; therapeutic target; tumor growth

Research Summary: The mechanism by which the prostate cancer cells colonize the bone environment and develop resistance to prevent or treat prostate cancer bone metastasis is critical to increase the survival rate of advanced prostate cancer patients. Annexin A2 (AnxA2) protein is overexpressed in metastatic prostate tumors and promotes cell migration and invasion by activating plasminogen and cleaving extracellular matrix. AnxA2 plays a critical role in hematopoietic stem cell localization to the marrow niche. AnxA2 serves as an adhesion molecule and regulates osteogenic differentiation, yet the molecular mechanisms remain unclear. We hypothesize that PTEN loss or mutation causes the increased translocation of AnxA2 to the outer cell surface which promotes prostate tumor metastasis to bone. The rationale for this hypothesis is based on our findings that demonstrated the higher expression of cell surface AnxA2 in PTEN null or mutated prostate cancer cell lines compared to wild-type PTEN prostate cancer cell lines because of increased phosphorylation of AnxA2 at Tyr-23 in PTEN null or mutated prostate cancer cell lines. The goal of the proposed study is to establish the correlation between PTEN loss and increased cell surface expression of AnxA2 in prostate cancer. In addition, we will establish that AnxA2 is an important phenomenon for prostate tumor bone metastasis. The proposed work will enhance our understanding on the role of cell surface AnxA2 in prostate cancer bone metastasis and could potentially be used as an important therapeutic target. The proposed work will provide the stepping stones for the development of a novel targeted therapy that may translate into an effective treatment regimen against advanced prostate cancer.

研究总结： 前列腺癌细胞在骨环境中定植并产生耐药性的机制 预防或治疗前列腺癌骨转移是提高晚期前列腺生存率的关键 癌症患者。膜联蛋白A2（AnxA2）蛋白在转移性前列腺肿瘤中过表达并促进细胞增殖 通过激活纤溶酶原和裂解细胞外基质来迁移和侵袭。AnxA2起着关键作用 在造血干细胞定位到骨髓龛中。AnxA2作为粘附分子， 调节成骨分化，但分子机制仍不清楚。我们假设， 缺失或突变导致AnxA2向细胞外表面的易位增加， 肿瘤转移到骨。这一假设的基本原理是基于我们的研究结果，表明 与野生型相比，PTEN缺失或突变的前列腺癌细胞系中细胞表面AnxA2的表达 PTEN前列腺癌细胞系，因为在PTEN缺失或缺失的细胞中， 突变的前列腺癌细胞系。这项研究的目的是建立PTEN与肿瘤细胞凋亡之间的相关性。 前列腺癌中AnxA2缺失和细胞表面表达增加。此外，我们将确定， AnxA2是前列腺肿瘤骨转移的重要现象。拟议的工作将加强我们的 了解细胞表面AnxA2在前列腺癌骨转移中的作用， 作为重要的治疗靶点。拟议的工作将提供垫脚石， 开发一种新的靶向治疗，可转化为有效的治疗方案， 前列腺癌