{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:14:53Z","timestamp":1789852493483,"version":"4.0.1"},"reference-count":31,"publisher":"Bioscientifica","issue":"10","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p>\n                    Pheochromocytomas (Pheos) and paragangliomas (PGLs) are neuroendocrine tumors. Approximately 30\u201340% of Pheos\/PGLs are due to germline mutations in one of the susceptibility genes, including those encoding the succinate dehydrogenase subunits A-D (\n                    <jats:italic>SDHA-D<\/jats:italic>\n                    ). Up to 2\/3 of patients affected by\n                    <jats:italic>SDHB<\/jats:italic>\n                    mutated Pheo\/PGL develop metastatic disease with no successful cure at present. Here, for the first time, we evaluated the effects of\n                    <jats:italic>SDHB<\/jats:italic>\n                    silencing in a three dimension (3D) culture using spheroids of a mouse Pheo cell line silenced or not (wild type\/wt\/control) for the SDHB subunit. We investigated the role of the microenvironment on spheroid growth and migration\/invasion by co-culturing\n                    <jats:italic>SDHB<\/jats:italic>\n                    -silenced or wt spheroids with primary cancer-activated fibroblasts (CAFs). When spheroids were co-cultured with fibroblasts,\n                    <jats:italic>SDHB<\/jats:italic>\n                    -silenced cells showed a significant increase in matrigel invasion as demonstrated by the computation of the migratory areas (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Moreover, cells detaching from the\n                    <jats:italic>SDHB<\/jats:italic>\n                    -silenced spheroids moved collectively, unlike the cells of wt spheroids that moved individually. Additionally,\n                    <jats:italic>SDHB-<\/jats:italic>\n                    silenced spheroids developed long filamentous formations along which clusters of cells migrated far away from the spheroid, whereas these structures were not present in wt spheroids. We found that lactate, largely secreted by CAFs, plays a specific role in promoting migration only of\n                    <jats:italic>SDHB<\/jats:italic>\n                    -silenced cells. In this study, we demonstrated that\n                    <jats:italic>SDHB<\/jats:italic>\n                    silencing\n                    <jats:italic>per se<\/jats:italic>\n                    increases tumor cell migration\/invasion and that microenvironment, as represented by CAFs, plays a pivotal role in enhancing collective migration\/invasion in Pheo\n                    <jats:italic>SDHB<\/jats:italic>\n                    -silenced tumor cells, suggesting their role in increasing the tumor metastasizing potential.\n                  <\/jats:p>","DOI":"10.1530\/erc-17-0212","type":"journal-article","created":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T20:10:56Z","timestamp":1503432656000},"page":"555-564","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":30,"title":["The microenvironment induces collective migration in SDHB-silenced mouse pheochromocytoma spheroids"],"prefix":"10.1530","volume":"24","author":[{"given":"Vanessa","family":"D'Antongiovanni","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Richter","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Canu","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Guasti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Mello","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Romagnoli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Pacak","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Eisenhofer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Mannelli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Rapizzi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Endocrine-Related Cancer","first-page":"T71","article-title":"15 YEARS OF PARAGANGLIOMA: Genetics and mechanism of pheochromocytoma-paraganglioma syndromes characterized by germline SDHB and SDHD mutations","volume":"22","author":"Baysal","year":"2015","unstructured":"Baysal BE Maher ER 2015 15 YEARS OF PARAGANGLIOMA: Genetics and mechanism of pheochromocytoma-paraganglioma syndromes characterized by germline SDHB and SDHD mutations. 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(doi:10.1016\/j.tcb.2014.11.006)"},{"key":"bib16","series-title":"Journal of Cellular Biochemistry","first-page":"2544","article-title":"Cancer cytokines and the relevance of 3D cultures for studying those implicated in human cancers.","volume":"118","author":"Maddaly","year":"2017","unstructured":"Maddaly R Subramaniyan A Balasubramanian H 2017 Cancer cytokines and the relevance of 3D cultures for studying those implicated in human cancers. Journal of Cellular Biochemistry 118 2544\u20132558. (doi:10.1002\/jcb.25970)"},{"key":"bib17","series-title":"Clinical and Experimental Metastasis","first-page":"239","article-title":"Characterization of an animal model of aggressive metastatic pheochromocytoma linked to a specific gene signature","volume":"26","author":"Martiniova","year":"2009","unstructured":"Martiniova L Lai EW Elkahloun AG Abu-Asab M Wickremasinghe A Solis DC Perera SM Huynh TT Lubensky IA Tischler AS 2009 Characterization of an animal model of aggressive metastatic pheochromocytoma linked to a specific gene signature. Clinical and Experimental Metastasis 26 239\u2013250. (doi:10.1007\/s10585-009-9236-0)"},{"key":"bib18","series-title":"Nature Reviews Molecular Cell Biology","first-page":"839","article-title":"The third dimension bridges the gap between cell culture and live tissue","volume":"8","author":"Pampaloni","year":"2007","unstructured":"Pampaloni F Reynaud EG Stelzer EHK 2007 The third dimension bridges the gap between cell culture and live tissue. 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(doi:10.1016\/j.pharmthera.2012.10.003)"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/24\/10\/ERC-17-0212.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/24\/10\/ERC-17-0212.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/24\/10\/ERC-17-0212.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:54:21Z","timestamp":1784555661000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/24\/10\/555-564\/25171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10]]},"references-count":31,"journal-issue":{"issue":"10"},"URL":"https:\/\/doi.org\/10.1530\/erc-17-0212","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10]]}}}