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

基本信息

批准号：
9789223
负责人：
PankaJ Chaudhary
金额：
$ 5.96万
依托单位：
UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9789223
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 Chromosomes, Human, Pair 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 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

项目摘要

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.

研究摘要：前列腺癌细胞在骨环境中定居并发展抗性的机制预防或治疗前列腺癌骨转移对于提高晚期前列腺的存活率至关重要癌症患者。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通过激活纤溶酶原和裂解细胞外基质来迁移和侵袭。 Anxa2起关键作用在造血干细胞定位到骨髓生态位。 Anxa2用作粘附分子，并且调节成骨分化，但分子机制尚不清楚。我们假设PTEN 损失或突变导致Anxa2易位到外部细胞表面，以促进前列腺肿瘤转移向骨骼。该假设的基本原理是基于我们的发现，证明了较高的与野生型相比 PTEN前列腺癌细胞系，因为在PTEN NULL或突变的前列腺癌细胞系。拟议的研究的目的是建立PTEN之间的相关性前列腺癌中Anxa2的损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。拟议的工作将增强我们的了解细胞表面Anxa2在前列腺癌骨转移中的作用，并有可能是用作重要的治疗靶点。拟议的工作将为开发一种新型的靶向疗法，该治疗可能转化为有效的治疗方案前列腺癌。