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  1. Article ; Online: Fibroblast heterogeneity in solid tumors: From single cell analysis to whole-body imaging.

    Peltier, Agathe / Seban, Romain-David / Buvat, Irène / Bidard, François-Clément / Mechta-Grigoriou, Fatima

    Seminars in cancer biology

    2022  Volume 86, Issue Pt 3, Page(s) 262–272

    Abstract: Cancer-Associated Fibroblasts (CAFs) represent the most prominent component of the tumor microenvironment (TME). Recent studies demonstrated that CAF are heterogeneous and composed of different subpopulations exerting distinct functions in cancer. CAF ... ...

    Abstract Cancer-Associated Fibroblasts (CAFs) represent the most prominent component of the tumor microenvironment (TME). Recent studies demonstrated that CAF are heterogeneous and composed of different subpopulations exerting distinct functions in cancer. CAF populations differentially modulate various aspects of tumor growth, including cancer cell proliferation, extra-cellular matrix remodeling, metastatic dissemination, immunosuppression and resistance to treatment. Among other markers, the Fibroblast Activation Protein (FAP) led to the identification of a specific CAF subpopulation involved in metastatic spread and immunosuppression. Expression of FAP at the surface of CAF is detected in many different cancer types of poor prognosis. Thus, FAP recently appears as an appealing target for therapeutic and molecular imaging applications. In that context,
    MeSH term(s) Humans ; Gelatinases/metabolism ; Positron Emission Tomography Computed Tomography/methods ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Single-Cell Analysis ; Whole Body Imaging ; Membrane Proteins/metabolism ; Neoplasms/diagnostic imaging ; Neoplasms/metabolism ; Fibroblasts/metabolism ; Tumor Microenvironment
    Chemical Substances Gelatinases (EC 3.4.24.-) ; Serine Endopeptidases (EC 3.4.21.-) ; Membrane Proteins
    Language English
    Publishing date 2022-04-27
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1033980-2
    ISSN 1096-3650 ; 1044-579X
    ISSN (online) 1096-3650
    ISSN 1044-579X
    DOI 10.1016/j.semcancer.2022.04.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Deciphering the spatial landscape and plasticity of immunosuppressive fibroblasts in breast cancer.

    Croizer, Hugo / Mhaidly, Rana / Kieffer, Yann / Gentric, Geraldine / Djerroudi, Lounes / Leclere, Renaud / Pelon, Floriane / Robley, Catherine / Bohec, Mylene / Meng, Arnaud / Meseure, Didier / Romano, Emanuela / Baulande, Sylvain / Peltier, Agathe / Vincent-Salomon, Anne / Mechta-Grigoriou, Fatima

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2806

    Abstract: Although heterogeneity of FAP+ Cancer-Associated Fibroblasts (CAF) has been described in breast cancer, their plasticity and spatial distribution remain poorly understood. Here, we analyze trajectory inference, deconvolute spatial transcriptomics at ... ...

    Abstract Although heterogeneity of FAP+ Cancer-Associated Fibroblasts (CAF) has been described in breast cancer, their plasticity and spatial distribution remain poorly understood. Here, we analyze trajectory inference, deconvolute spatial transcriptomics at single-cell level and perform functional assays to generate a high-resolution integrated map of breast cancer (BC), with a focus on inflammatory and myofibroblastic (iCAF/myCAF) FAP+ CAF clusters. We identify 10 spatially-organized FAP+ CAF-related cellular niches, called EcoCellTypes, which are differentially localized within tumors. Consistent with their spatial organization, cancer cells drive the transition of detoxification-associated iCAF (Detox-iCAF) towards immunosuppressive extracellular matrix (ECM)-producing myCAF (ECM-myCAF) via a DPP4- and YAP-dependent mechanism. In turn, ECM-myCAF polarize TREM2+ macrophages, regulatory NK and T cells to induce immunosuppressive EcoCellTypes, while Detox-iCAF are associated with FOLR2+ macrophages in an immuno-protective EcoCellType. FAP+ CAF subpopulations accumulate differently according to the invasive BC status and predict invasive recurrence of ductal carcinoma in situ (DCIS), which could help in identifying low-risk DCIS patients eligible for therapeutic de-escalation.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Fibroblasts/pathology ; Cancer-Associated Fibroblasts/pathology ; Extracellular Matrix/pathology ; Tumor Microenvironment ; Folate Receptor 2
    Chemical Substances FOLR2 protein, human ; Folate Receptor 2
    Language English
    Publishing date 2024-04-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-47068-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma.

    Thirant, Cécile / Peltier, Agathe / Durand, Simon / Kramdi, Amira / Louis-Brennetot, Caroline / Pierre-Eugène, Cécile / Gautier, Margot / Costa, Ana / Grelier, Amandine / Zaïdi, Sakina / Gruel, Nadège / Jimenez, Irène / Lapouble, Eve / Pierron, Gaëlle / Sitbon, Déborah / Brisse, Hervé J / Gauthier, Arnaud / Fréneaux, Paul / Grossetête, Sandrine /
    Baudrin, Laura G / Raynal, Virginie / Baulande, Sylvain / Bellini, Angela / Bhalshankar, Jaydutt / Carcaboso, Angel M / Geoerger, Birgit / Rohrer, Hermann / Surdez, Didier / Boeva, Valentina / Schleiermacher, Gudrun / Delattre, Olivier / Janoueix-Lerosey, Isabelle

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 2575

    Abstract: Noradrenergic and mesenchymal identities have been characterized in neuroblastoma cell lines according to their epigenetic landscapes and core regulatory circuitries. However, their relationship and relative contribution in patient tumors remain poorly ... ...

    Abstract Noradrenergic and mesenchymal identities have been characterized in neuroblastoma cell lines according to their epigenetic landscapes and core regulatory circuitries. However, their relationship and relative contribution in patient tumors remain poorly defined. We now document spontaneous and reversible plasticity between the two identities, associated with epigenetic reprogramming, in several neuroblastoma models. Interestingly, xenografts with cells from each identity eventually harbor a noradrenergic phenotype suggesting that the microenvironment provides a powerful pressure towards this phenotype. Accordingly, such a noradrenergic cell identity is systematically observed in single-cell RNA-seq of 18 tumor biopsies and 15 PDX models. Yet, a subpopulation of these noradrenergic tumor cells presents with mesenchymal features that are shared with plasticity models, indicating that the plasticity described in these models has relevance in neuroblastoma patients. This work therefore emphasizes that intrinsic plasticity properties of neuroblastoma cells are dependent upon external cues of the environment to drive cell identity.
    MeSH term(s) Humans ; Cell Plasticity ; Neuroblastoma/metabolism ; Cell Line, Tumor ; Tumor Microenvironment/genetics
    Language English
    Publishing date 2023-05-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-38239-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Author Correction: Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes.

    Rombaut, Dries / Chiu, Hua-Sheng / Decaesteker, Bieke / Everaert, Celine / Yigit, Nurten / Peltier, Agathe / Janoueix-Lerosey, Isabelle / Bartenhagen, Christoph / Fischer, Matthias / Roberts, Stephen / D'Haene, Nicky / De Preter, Katleen / Speleman, Frank / Denecker, Geertrui / Sumazin, Pavel / Vandesompele, Jo / Lefever, Steve / Mestdagh, Pieter

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 10536

    Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. ...

    Abstract A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
    Language English
    Publishing date 2019-07-17
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-46785-6
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  5. Article ; Online: Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes.

    Rombaut, Dries / Chiu, Hua-Sheng / Decaesteker, Bieke / Everaert, Celine / Yigit, Nurten / Peltier, Agathe / Janoueix-Lerosey, Isabelle / Bartenhagen, Christoph / Fischer, Matthias / Roberts, Stephen / D'Haene, Nicky / De Preter, Katleen / Speleman, Frank / Denecker, Geertrui / Sumazin, Pavel / Vandesompele, Jo / Lefever, Steve / Mestdagh, Pieter

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 5685

    Abstract: Long intergenic non-coding RNAs (lincRNAs) are emerging as integral components of signaling pathways in various cancer types. In neuroblastoma, only a handful of lincRNAs are known as upstream regulators or downstream effectors of oncogenes. Here, we ... ...

    Abstract Long intergenic non-coding RNAs (lincRNAs) are emerging as integral components of signaling pathways in various cancer types. In neuroblastoma, only a handful of lincRNAs are known as upstream regulators or downstream effectors of oncogenes. Here, we exploit RNA sequencing data of primary neuroblastoma tumors, neuroblast precursor cells, neuroblastoma cell lines and various cellular perturbation model systems to define the neuroblastoma lincRNome and map lincRNAs up- and downstream of neuroblastoma driver genes MYCN, ALK and PHOX2B. Each of these driver genes controls the expression of a particular subset of lincRNAs, several of which are associated with poor survival and are differentially expressed in neuroblastoma tumors compared to neuroblasts. By integrating RNA sequencing data from both primary tumor tissue and cancer cell lines, we demonstrate that several of these lincRNAs are expressed in stromal cells. Deconvolution of primary tumor gene expression data revealed a strong association between stromal cell composition and driver gene status, resulting in differential expression of these lincRNAs. We also explored lincRNAs that putatively act upstream of neuroblastoma driver genes, either as presumed modulators of driver gene activity, or as modulators of effectors regulating driver gene expression. This analysis revealed strong associations between the neuroblastoma lincRNAs MIAT and MEG3 and MYCN and PHOX2B activity or expression. Together, our results provide a comprehensive catalogue of the neuroblastoma lincRNome, highlighting lincRNAs up- and downstream of key neuroblastoma driver genes. This catalogue forms a solid basis for further functional validation of candidate neuroblastoma lincRNAs.
    MeSH term(s) Cell Line, Tumor ; Gene Drive Technology/methods ; Gene Expression Profiling/methods ; Humans ; Neural Stem Cells/physiology ; Neuroblastoma/genetics ; RNA, Long Noncoding/genetics ; Sequence Analysis, RNA/methods ; Signal Transduction/genetics ; Transcription Factors/genetics
    Chemical Substances RNA, Long Noncoding ; Transcription Factors
    Language English
    Publishing date 2019-04-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-42107-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

    Boeva, Valentina / Louis-Brennetot, Caroline / Peltier, Agathe / Durand, Simon / Pierre-Eugène, Cécile / Raynal, Virginie / Etchevers, Heather C / Thomas, Sophie / Lermine, Alban / Daudigeos-Dubus, Estelle / Geoerger, Birgit / Orth, Martin F / Grünewald, Thomas G P / Diaz, Elise / Ducos, Bertrand / Surdez, Didier / Carcaboso, Angel M / Medvedeva, Irina / Deller, Thomas /
    Combaret, Valérie / Lapouble, Eve / Pierron, Gaelle / Grossetête-Lalami, Sandrine / Baulande, Sylvain / Schleiermacher, Gudrun / Barillot, Emmanuel / Rohrer, Hermann / Delattre, Olivier / Janoueix-Lerosey, Isabelle

    Nature genetics

    2017  Volume 49, Issue 9, Page(s) 1408–1413

    Abstract: Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed ... ...

    Abstract Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.
    MeSH term(s) Animals ; Blotting, Western ; Cell Line, Tumor/classification ; Cell Lineage/drug effects ; Cell Lineage/genetics ; Doxycycline/pharmacology ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/genetics ; Genetic Heterogeneity ; HEK293 Cells ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Neuroblastoma/drug therapy ; Neuroblastoma/genetics ; Neuroblastoma/metabolism ; RNA Interference ; RNAi Therapeutics ; Reverse Transcriptase Polymerase Chain Reaction ; Single-Cell Analysis ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Xenograft Model Antitumor Assays/methods
    Chemical Substances Homeodomain Proteins ; NBPhox protein ; Transcription Factors ; Doxycycline (N12000U13O)
    Language English
    Publishing date 2017-07-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/ng.3921
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3613: Show issues Location:
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    Zs.MG 46: Show issues

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