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Heparan Sulfate in Prostate Cancer

硫酸乙酰肝素在前列腺癌中的作用

基本信息

批准号：
9914542
负责人：
Houjian Cai
金额：
$ 56.17万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-13 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9914542
关键词：
Ablation Advanced Development Affect Anabolism Biochemical Bioinformatics Biological Assay CXCR4 gene Cancer Cell Growth Cancer Etiology Cancerous Cell physiology Cell surface Cells Cellular Structures Cessation of life Coupled Development Disease EXT1 gene Early Diagnosis Environment Enzymes Epithelial Cells Epitopes Event Extracellular Matrix FGF1 gene FGFR1 gene Gene Expression Genes Genetic Growth Heparitin Sulfate Human IL8RB gene In Vitro Infiltration Inflammation Inflammatory Investigation Knock-out Life Ligands Malignant Neoplasms Malignant neoplasm of prostate Measures Modeling Molecular Mus Mutate Myeloid-derived suppressor cells Play Polymers Polysaccharides Prostate Prostate Cancer therapy Prostatic Proteins Public Health Reporting Role Signal Transduction Specificity Specimen Structure System Testing Treatment Efficacy Tumor Suppressor Genes Xenograft procedure autocrine cancer initiation cell motility chemokine in vivo men mouse model neutralizing antibody novel novel marker novel therapeutics outcome forecast overexpression prostate cancer cell prostate cancer cell line prostate cancer model public health relevance recruit tumor tumor progression tumorigenesis

项目摘要

PROJECT SUMMARY Prostate cancer (PCa) is one of the most prevalent forms of malignancy and the second most common cause of cancer-related death in men. Uncovering novel mechanisms that control prostatic tumorigenesis may advance development of more effective therapeutics to treat this life-threatening disease. Heparan sulfate (HS), a type of polysaccharide, is an essential component of the cell microenvironment and plays an important role in cell-cell and cell-matrix interaction and signaling. Recent studies reported that expression of HS-synthesizing and modifying genes are dysregulated in human PCa specimens. Currently, it is not known what causes this aberrant HS expression, and, more importantly, what are the functional consequences of the aberrant HS expression in prostatic tumorigenesis. In this application, we propose to test our novel hypothesis “Pten-loss in prostate leads to aberrant HS expression creating a unique cellular environment that potentiates prostatic tumorigenesis” by pursuing the following three Specific Aims: 1. Determine if aberrant HS expression in human prostate epithelial cells is induced by Pten-loss and correlates with malignancy of Pten- null human PCa; 2. Determine if aberrant HS expression induced by Pten-loss potentiates prostatic tumorigenesis; 3. Determine if aberrant HS expression induced by Pten-loss potentiates PCa-associated inflammation. The proposed studies will use both novel and established genetic, cellular, biochemical and bioinformatics approaches in conjunction with in vitro cell function and in vivo human and mouse PCa models. These serial investigations are anticipated to delineate a novel mechanism that drives aberrant HS expression in PCa, reveal the aberrant HS expression to be a novel biomarker for PCa early diagnosis and prognosis, and elucidate the pivotal roles and their underlying molecular mechanisms of the aberrant HS expression in prostatic tumorigenesis, which likely will contribute to the development of novel therapeutics for PCa treatment.

项目总结