Exosomes: A novel mechanism for bladder cancer tumorigenesis and progression
外泌体:膀胱癌肿瘤发生和进展的新机制
基本信息
- 批准号:8649159
- 负责人:
- 金额:$ 34.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-01-08 至 2018-12-31
- 项目状态:已结题
- 来源:
- 关键词:AffectBehaviorBindingBiochemicalBiologicalBiological MarkersBiological ProcessBiologyBladderCancer BiologyCancer PatientCell CommunicationCell ProliferationCellsCommunicationDatabasesDevelopmentDiagnosisDiseaseDisease ProgressionElderlyEpidermal Growth Factor ReceptorGene ExpressionGenesGenetic MarkersGoalsImplantIncidenceLeadLinkMalignant NeoplasmsMalignant neoplasm of urinary bladderMass Spectrum AnalysisMediatingMembraneMessenger RNAMicroRNAsMolecularMolecular ProfilingMonitorMorbidity - disease rateMusMuscleNatureNude MicePTK2 genePathway interactionsPatientsPhosphorylationPhosphotransferasesPlayPropertyProteinsRecurrenceRoleSeriesSignal TransductionSignaling MoleculeStagingSurvival RateTestingTransurethral ResectionTumor BiologyUltrasonographyUnited StatesUrineUrologic DiseasesUrothelial CellVesicleangiogenesisbasecancer cellcancer geneticscell motilitycell typeextracellularin vivointerestknock-downmortalitymouse modelnovelnovel diagnosticsparacrinepreventprognosticprotein activationprotein profilingpublic health relevancesample collectionscreeningtheoriestherapeutic targettumortumor growthtumor progressiontumorigenesisurinary
项目摘要
Bladder cancer (BC) is the fifth most commonly diagnosed malignancy in the United States.
The majority of BC patients have non-muscle invasive (NMI) disease, and these tumors frequently
recur after transurethral resection of initial tumors. Approximately 25-30% of BC patients have muscle
invasive disease (MIBC). Unfortunately, 50% of MI BC patients will develop metastatic disease with
10% five year survival rate. This high recurrence rate in NMI BC, and high morbidity and mortality in
MI BC make it one of the most burdensome cancers to manage and treat. Therefore, there is a great
need for understanding the underlying biology of these tumors which would lead to the development
of stage specific therapeutic targets to prevent tumor recurrence and progression.
Small extracellular membrane bound vesicles, termed exosomes, can be secreted from
numerous types of cells taken up by neighboring cells, consequently affecting their behaviors. There
is increasing evidence supporting the theory that cancer exosomes play vital roles in many steps of
cancer development and progression. Preliminary studies showed that BC exosomes promote BC
cell migration, invasion and angiogenesis. Several BC exosome proteins were identified, among
which EDIL-3 is found to be over-expressed in BC exosomes as compared to normal controls, and
knocking down EDIL3 reduced cancer exosome-mediated BC cell migration and angiogenesis.
Mechanistic studies indicated that EDIL-3 can activate the transmembrane kinases such as FAK and
EGFR, consequently inducing a signal cascade to influence cell proliferation and migration. Based on
preliminary studies, we hypothesize that BC-derived exosomes, via the paracrine manner that
transfers cancer-associated proteins to recipient cells, consequently promote tumor progression.
Moreover, urinary exosome protein profiles from BC patients can serve as disease biomarkers.
Four Aims are proposed to study exosome roles in BC biology. Aim 1: To delineate underlying
mechanisms by which EDIL-3 promotes bladder progression. Aim 2: To study the roles of 8 cancer-
associated exosomal proteins on tumor progression. Aim 3: To determine the expression and function
of those cancer-associated proteins in urinary exosomes of BC patients. Aim 4: To study cancer
exosome ability to promote cancer progression in vivo. Our long-term goal is to understand the
biological functions of cancer exosomes and to reveal possible novel treatment targets.
膀胱癌(BC)是美国第五大最常诊断的恶性肿瘤。
项目成果
期刊论文数量(0)
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{{ truncateString('YI-FEN LEE', 18)}}的其他基金
Exosomes: A novel mechanism for bladder cancer tumorigenesis and progression
外泌体:膀胱癌肿瘤发生和进展的新机制
- 批准号:
8986775 - 财政年份:2014
- 资助金额:
$ 34.68万 - 项目类别:
Exosomes: A novel mechanism for bladder cancer tumorigenesis and progression
外泌体:膀胱癌肿瘤发生和进展的新机制
- 批准号:
8790431 - 财政年份:2014
- 资助金额:
$ 34.68万 - 项目类别:
TR4 orphan receptor, a longevity assurance gene, in prostate carcinogenesis
TR4孤儿受体,一种长寿保证基因,在前列腺癌发生中的作用
- 批准号:
8104240 - 财政年份:2008
- 资助金额:
$ 34.68万 - 项目类别:
TR4 orphan receptor, a longevity assurance gene, in prostate carcinogenesis
TR4孤儿受体,一种长寿保证基因,在前列腺癌发生中的作用
- 批准号:
7899998 - 财政年份:2008
- 资助金额:
$ 34.68万 - 项目类别:
TR4 orphan receptor, a longevity assurance gene, in prostate carcinogenesis
TR4孤儿受体,一种长寿保证基因,在前列腺癌发生中的作用
- 批准号:
7522530 - 财政年份:2008
- 资助金额:
$ 34.68万 - 项目类别:
TR4 orphan receptor, a longevity assurance gene, in prostate carcinogenesis
TR4孤儿受体,一种长寿保证基因,在前列腺癌发生中的作用
- 批准号:
8300200 - 财政年份:2008
- 资助金额:
$ 34.68万 - 项目类别:
TR4 orphan receptor, a longevity assurance gene, in prostate carcinogenesis
TR4孤儿受体,一种长寿保证基因,在前列腺癌发生中的作用
- 批准号:
7682233 - 财政年份:2008
- 资助金额:
$ 34.68万 - 项目类别:
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