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
总结
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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资助金额:$40.0万
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负责人:Besim Ogretmen
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依托单位:
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财政年份:2020
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负责人:Besim Ogretmen
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依托单位:
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批准号:9930853
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项目类别:
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资助金额:$1.62万
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财政年份:2019
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负责人:Besim Ogretmen
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依托单位:
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项目类别:
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依托单位:
Ceramide metabolism and the regulation of PD-L1 signaling to control metastasis and resistance to immunotherapy in TNBC
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批准号:10801345
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项目类别:
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资助金额:$37.11万
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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: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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批准号:9072008
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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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批准号:9980696
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项目类别:
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资助金额:$174.77万
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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:
Mechanisms of sphingolipid analogue drug FTY720-mediated NSCLC tumor suppression
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批准号:8585322
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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: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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负责人:Besim Ogretmen
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依托单位:
COBRE in Lipidomics and Pathobiology
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批准号:8714006
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项目类别:
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资助金额:$109.48万
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财政年份:2012
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负责人:Besim Ogretmen
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依托单位:
COBRE in Lipidomics and Pathobiology
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批准号:8514026
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项目类别:
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资助金额:$105.65万
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财政年份:2012
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负责人:Besim Ogretmen
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依托单位:
COBRE in Lipidomics and Pathobiology
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批准号:8305278
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项目类别:
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资助金额:$109.48万
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财政年份:2012
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负责人:Besim Ogretmen
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依托单位:
COBRE in Lipidomics and Pathobiology
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批准号:9098741
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项目类别:
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资助金额:$109.48万
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财政年份:2012
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负责人:Besim Ogretmen
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依托单位:
Lipidomics Shared Resource
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批准号:10377471
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项目类别:
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资助金额:$6.18万
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财政年份:2009
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负责人:Besim Ogretmen
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依托单位:
Developmental Cancer Therapeutics
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批准号:10589910
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项目类别:
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资助金额:$5.06万
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财政年份:2009
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负责人:Besim Ogretmen
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依托单位:
海外基金