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                <a href="#">This page in English</a>
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                <h1 class="mt-0 mb-3 mb-lg-5">Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors
                    revealed by targeting of
                    PDGF-DD.</h1>
                <h2 class="h6">Författare</h2>
                <p>
                    <a href="#">Eliane Cortez</a><br>
                    <a href="#">Hanna Gladh</a><br>
                    <a href="#">Sebastian Braun</a><br>
                    <a href="#">Matteo Bocci</a><br>
                    Eugenia Cordero<br>
                    Niklas K Björkström<br>
                    Hideki Miyazaki<br>
                    Iacovos P Michael<br>
                    Ulf Eriksson<br>
                    Erika Folestad<br>
                    Kristian Pietras
                </p>
                <h2>Sammanfattning på Engelska</h2>
                <p>Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for
                    cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating
                    distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment
                    response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the
                    development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib.
                    The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility
                    of a previously unidentified signaling pathway involved in tumor development. However, the precise function of
                    PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout
                    mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in
                    pancreatic neuroendocrine tumors (PanNET).</p>
                <p>Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly,
                    ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD
                    stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous
                    malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells
                    characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we
                    demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the
                    PDGF-DD/PDGFRβ axis.</p>
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                <div class="infobox bg-copper-50">
                    <p>
                        <strong>Avdelning/ar:</strong><br>
                        <a href="#">Avdelningen för translationell cancerforskning</a><br>
                        <a href="#">Experimentell onkologi</a>
                    </p>
                    <p><strong>Publiceringsår:</strong> 2016</p>
                    <p><strong>Språk:</strong> Engelska</p>
                    <p><strong>Sidor:</strong> 864-873</p>
                    <p><strong>Publikation/Tidskrift/Serie:</strong> Proceedings of the National Academy of Sciences</p>
                    <p><strong>Volym:</strong> 113</p>
                    <p><strong>Nummer:</strong> 7</p>
                    <p><strong>Fulltext:</strong><br>
                        <a href="#">Tillgänglig som fulltext</a><br>
                        <a href="#">Nedladdningsstatistik</a>
                    </p>
                    <p>
                        <strong>Länkar:</strong><br>
                        <a href="#">Exempellänk</a>
                    </p>
                    <p><strong>Dokumenttyp:</strong> Artikel i tidskrift</p>
                    <p><strong>Förlag:</strong> National Acad Sciences</p>
                </div>

                <div class="infobox bg-sky-50">
                    <p>
                        <strong>Ämne</strong><br>
                        Cancer and Oncology
                    </p>
                    <p>
                        <strong>Status</strong><br>
                        Published
                    </p>
                    <p>
                        <strong>Forskningsgrupp</strong><br>
                        Experimental oncology
                    </p>
                    <p>
                        <strong>ISBN/ISSN/Andra:</strong><br>
                        ISSN: 1091-6490
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