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TP Tumor-Stroma Interactions

TP Tumor-Stroma Interactions. Tumor and plasma proteomics insights into tumor stroma interactions 109 luminal human breast cancer specimens+plasma high levels of Amphiregulin (AREG) in undissected tumor specimens

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TP Tumor-Stroma Interactions

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  1. TP Tumor-Stroma Interactions • Tumor andplasmaproteomics • insightsintotumorstromainteractions • 109 luminal human breastcancerspecimens+plasma • highlevelsofAmphiregulin (AREG) in undissectedtumorspecimens • EGF not detectable in tumorspecimens: Human plasmasamples (healthy & diseased) showhigh but variable yieldsof HRG, BTC, EGF andmanyother ligands • Tumor VEGFAlevelscorrelatewithrisk/grading • Tumor HGFshows inverse correlationwithrisk/grading • Stromaldownregulationof Caveolin-1 correlateswithrisk VEGFA HGF

  2. TP Tumor-Stroma Interactions • Tumor andplasmaproteomics • insightsintotumorstromainteractions • 109 luminal human breastcancerspecimens+plasma • Molecularimpactof e.g. AREG and EGF on (A) downstreamsignaling, (B) transcriptionfactoractivation/expressionand (C) induction/repressionof miRs in model systemsof human breastcancer • Systems biologyofcrosstalkbetweenInsulinR/IGFR and EGFR signals, integrationofcytokinesignaling • WhatinitiatesthedownregulationofCaveolin-1 in stromacells (CAF)? • Proteomeprofilingofothermolecularsubtypesof human breastcancer (HER2 pos., TN, basal)

  3. Inflammatorycytokines IL-1, IL6, IL-8, TNFα, TGFβ, VEGFA, … Growth factors AREG, EGF, HGF, IGF-1… WP2 Modeling of ligand-specificsignaling(e.g. EGF vs. AREG), integrationofinsulinandcytokinesignaling Readout: (1) mRNA/Illumina (2) RPPA (3) TF enrichmentfor RPPA (nuclei)  identifycooperativeeffectsbetweensignalingnodes, molecularsubtype-specific  validationofcrosstalkeffects in co-culturemodels TP Tumor-Stroma Interactions WP1 Cytokine, proteome, & GF profilesof human breastcancerspecimens → identifytargetsfor WP2 Basal, HER2+, triple negative breastcancer apoptosis WNT celladhesion TGFb/SMAD cellcycle 12 corepathwaysinvolved in cancer „kinase dynamicsinvolved in transcriptionfactoractivationandfeedbackcontrolsofsignalingsystems“ RAS/RAF DNA damage • WP3 data-drivendevelopmentof „tumor stroma“ treatmentconcepts • validation in co-culturemodels • validation in human tumors (IHC, RPPA) metabolictransformation PI3K/PTEN WP4validate „tumor stroma“ treatmentconcepts in mousemodels → analysemousetumors, mouseplasmaproteomics → explanttumors/cellculture, measurecytokines, growthfactors Hedgehog NOTCH bloodvessels JAK/STAT fattytissue

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