{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Qin N"],"funding":["Research Commission of the Medical Faculty, Heinrich Heine University Düsseldorf","“Förderverein Löwenstern”","Deutsche Forschungsgemeinschaft","José-Carreras Foundation","Fundação Millennium bcp and Fundação Amélia de Mello","German Cancer Aid","Elterninitiative Kinderkrebsklinik"],"pagination":["1509-1523"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9435486"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(9)"],"pubmed_abstract":["<h4>Background</h4>Intratumoral heterogeneity is crucially involved in metastasis, resistance to therapy, and cancer relapse. Amplifications of the proto-oncogene MYC display notable heterogeneity at the single-cell level and are associated with a particularly dismal prognosis in high-risk medulloblastomas (MBs). The aim of this study was to establish the relevance of interclonal cross-talk between MYC-driven and non-MYC-driven MB cells.<h4>Methods</h4>We used fluorescence in situ hybridization, single-cell transcriptomics, and immunohistochemistry, in vitro isogenic cell models, non-targeted proteomics, mass spectrometry-based metabolite quantification, HUVECs tube formation assay, and orthotopic in vivo experiments to investigate interclonal cross-talk in MB.<h4>Results</h4>We found that the release of lactate dehydrogenase A (LDHA) from MYC-driven cells facilitates metastatic seeding and outgrowth, while secretion of dickkopf WNT signaling pathway inhibitor 3 from non-MYC-driven cells promotes tumor angiogenesis. This tumor-supporting interaction between both subclones was abrogated by targeting the secretome through pharmacological and genetic inhibition of LDHA, which significantly suppressed tumor cell migration.<h4>Conclusion</h4>Our study reveals the functional relevance of clonal diversity and highlights the therapeutic potential of targeting the secretome to interrupt interclonal communication and progression in high-risk MB."],"journal":["Neuro-oncology"],"pubmed_title":["Intratumoral heterogeneity of MYC drives medulloblastoma metastasis and angiogenesis."],"pmcid":["PMC9435486"],"funding_grant_id":["FOKO 2019-06","KFO 337","TRR205","RE938/4-1","CRC/TRR 205","FOKO 2015-46","RE 2857/2-1","111537","DJCLS 21R/2019"],"pubmed_authors":["Qin N","Picard D","Bartl J","Remke M","Langini M","Borkhardt A","Blumel L","Custodia C","Eisenhofer G","Faria CC","Bechmann N","Barata JT","Stefanski A","Malzkorn B","Fischer U","Reifenberger G","Cascao R","Taban K","Gobbels S","Puget S","Paisana E","Felsberg J","Gravemeyer J","Stuhler K","Ayrault O","Meyer FD","Conrad C","Becker JC"],"additional_accession":[]},"is_claimable":false,"name":"Intratumoral heterogeneity of MYC drives medulloblastoma metastasis and angiogenesis.","description":"<h4>Background</h4>Intratumoral heterogeneity is crucially involved in metastasis, resistance to therapy, and cancer relapse. Amplifications of the proto-oncogene MYC display notable heterogeneity at the single-cell level and are associated with a particularly dismal prognosis in high-risk medulloblastomas (MBs). The aim of this study was to establish the relevance of interclonal cross-talk between MYC-driven and non-MYC-driven MB cells.<h4>Methods</h4>We used fluorescence in situ hybridization, single-cell transcriptomics, and immunohistochemistry, in vitro isogenic cell models, non-targeted proteomics, mass spectrometry-based metabolite quantification, HUVECs tube formation assay, and orthotopic in vivo experiments to investigate interclonal cross-talk in MB.<h4>Results</h4>We found that the release of lactate dehydrogenase A (LDHA) from MYC-driven cells facilitates metastatic seeding and outgrowth, while secretion of dickkopf WNT signaling pathway inhibitor 3 from non-MYC-driven cells promotes tumor angiogenesis. This tumor-supporting interaction between both subclones was abrogated by targeting the secretome through pharmacological and genetic inhibition of LDHA, which significantly suppressed tumor cell migration.<h4>Conclusion</h4>Our study reveals the functional relevance of clonal diversity and highlights the therapeutic potential of targeting the secretome to interrupt interclonal communication and progression in high-risk MB.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2025-04-21T17:16:14.559Z","creation":"2025-04-21T17:16:14.559Z"},"accession":"S-EPMC9435486","cross_references":{"pubmed":["35307743"],"doi":["10.1093/neuonc/noac068"]}}