Project 2: Regulation of Tumor Metastasis by Systemic S1P and Complement Signaling
Project 2: Regulation of Tumor Metastasis by Systemic S1P and Complement Signaling
批准号:
9072014
负责人:
Besim Ogretmen
金额:
$29.99万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-05-01 至 2021-04-30
关键词:
BRMS1 geneBiologicalBloodBlood CirculationBlood VesselsC5a anaphylatoxin receptorCancer Cell GrowthCell DeathCellsComplementComplement 5aCoupledDataDevelopmentEarly DiagnosisEndothelial CellsGTP-Binding ProteinsGeneticGoalsImmune systemKnock-outMalignant NeoplasmsMediatingMetastatic Neoplasm to the LungMolecularMonitorNeoplasm MetastasisOrganOrganismPathogenesisPatientsReceptor SignalingRegulationRoleSPHK1 enzymeSerumSerum MarkersSignal TransductionSiteSolid NeoplasmSourceSphingolipidsSphingosine-1-Phosphate ReceptorStreamTestingTreatment EfficacyVascular Endothelial CellWild Type Mouseattenuationbasecancer cellcell typecomplement systemdesignmigrationnovelnovel therapeuticsresponsesphingosine 1-phosphatetherapeutic targettumortumor growth
中文摘要
摘要
该项目旨在检验一种新的假设,即癌细胞通过C5a/C5aR与宿主通信-
诱导全身性SK1/S1P,进而促进肿瘤转移,并抑制全身性S1P/C5aR
信号转导抑制肿瘤转移。为了验证这一假设,提出了三个具体目标:目标1是设计的
目的:明确癌细胞诱导血管内皮细胞补体信号转导途径的作用和机制。
系统的SK1/S1P在肿瘤转移调控中的作用AIM 2旨在确定下游
癌细胞诱导系统SK-1/S1P促进肿瘤转移的机制在这个目标上,我们的
主要目的是验证我们的假设,即癌细胞诱导的系统性SK1/S1P抑制a基因的表达
主控转移抑制因子(BRMS1)通过S1PR2信号在癌细胞中发挥作用,诱导肿瘤转移。
AIM 3旨在确定靶向系统性S1P和/或C5a信号转导系统的治疗效果
肿瘤转移的减弱。在这个目标中,我们的主要目标是测试一个新的假设,即抑制
系统的C5aR/SK1/S1P信号通路将通过激活肿瘤BRMS1来抑制肿瘤转移。这些研究
将有助于揭示癌细胞如何通过SK1/S1P与宿主通信,并补充信号以
调节肿瘤转移,导致开发抑制肿瘤的新治疗策略
生长或转移。在这个项目中,我们还将确定患者系统性S1P/C5a的升高
晚期实体瘤将为监测治疗反应和/或早期提供新的血清标志物
进展到转移的检测。
英文摘要
SUMMARY
This project is designed to test a novel hypothesis that cancer cells communicate with the host via C5a/C5aR-
induced systemic SK1/S1P, which then promotes tumor metastasis, and that inhibition of systemic S1P/C5aR
signaling suppresses metastasis. To test this hypothesis, three Specific Aims are proposed: Aim 1 is designed
to define the roles and mechanisms of cancer cell-induced vascular endothelial cell complement signaling and
systemic SK1/S1P in the regulation of tumor metastasis. Aim 2 is designed to determine the down-stream
mechanisms by which cancer cell-induced systemic SK-1/S1P promotes tumor metastasis. In this Aim, our
main goal is to test our hypothesis that cancer cell-induced systemic SK1/S1P inhibits the expression of a
master suppressor of metastasis (BRMS1) via S1PR2 signaling in cancer cells, inducing tumor metastasis.
Aim 3 is designed to determine the therapeutic efficacy of targeting systemic S1P and/or C5a signaling for the
attenuation of tumor metastasis. In this Aim, our main goal is to test a novel hypothesis that inhibition of
systemic C5aR/SK1/S1P signaling will inhibit tumor metastasis via activation of tumor BRMS1. These studies
will help uncover how cancer cells communicate with the host via SK1/S1P and complement signaling to
regulate tumor metastasis, leading to the development of novel therapeutic strategies for the inhibition of tumor
growth or metastasis. In this project, we will also determine if the elevation of systemic S1P/C5a in patients
with advanced solid tumors will provide novel serum markers for monitoring response to therapy and/or early
detection of progression to metastasis.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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项目类别:
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财政年份:2018
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依托单位:
Ceramide metabolism and the regulation of TGF-beta receptor signaling to control metastasis
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批准号:9977980
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项目类别:
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资助金额:$34.2万
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财政年份:2018
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负责人:Besim Ogretmen
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依托单位:
Ceramide metabolism and the regulation of TGF-beta receptor signaling to control metastasis
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批准号:10222592
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项目类别:
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资助金额:$34.2万
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财政年份:2018
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负责人:Besim Ogretmen
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依托单位:
Ceramide metabolism and the regulation of TGF-beta receptor signaling to control metastasis
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批准号:10460230
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项目类别:
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资助金额:$33.51万
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财政年份:2018
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负责人:Besim Ogretmen
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依托单位:
Ceramide metabolism and the regulation of TGF-beta receptor signaling to control metastasis
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批准号:9441547
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项目类别:
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资助金额:$34.2万
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财政年份:2018
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负责人:Besim Ogretmen
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依托单位:
Development of Novel Cancer Therapeutics by Targeting Sphingolipid Signaling
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项目类别:
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资助金额:$181.11万
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财政年份:2016
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负责人:Besim Ogretmen
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依托单位:
Development of Novel Cancer Therapeutics by Targeting Sphingolipid Signaling
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项目类别:
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负责人:Besim Ogretmen
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依托单位:
Mechanisms of sphingolipid analogue drug FTY720-mediated NSCLC tumor suppression
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项目类别:
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财政年份:2013
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负责人:Besim Ogretmen
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依托单位:
Mechanisms of sphingolipid analogue drug FTY720-mediated NSCLC tumor suppression
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批准号:9269533
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项目类别:
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资助金额:$31.02万
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财政年份:2013
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负责人:Besim Ogretmen
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依托单位:
Mechanisms of sphingolipid analogue drug FTY720-mediated NSCLC tumor suppression
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批准号:9076632
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项目类别:
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资助金额:$31.02万
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财政年份:2013
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依托单位:
COBRE in Lipidomics and Pathobiology
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依托单位:
COBRE in Lipidomics and Pathobiology
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依托单位:
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资助金额:$109.48万
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依托单位:
COBRE in Lipidomics and Pathobiology
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资助金额:$109.48万
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Developmental Cancer Therapeutics
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依托单位:
海外基金