Reversible adaptive plasticity

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dc.contributor.author Abou-Antoun, Thamara
dc.contributor.author Chakrabati, Lina
dc.contributor.author Vykmanovic, Stainslav
dc.contributor.author Sandler, Anthony D.
dc.date.accessioned 2016-09-27T09:30:11Z
dc.date.available 2016-09-27T09:30:11Z
dc.date.copyright 2012 en_US
dc.identifier.issn 2234-943X en_US
dc.identifier.uri http://hdl.handle.net/10725/4418
dc.description.abstract We describe a novel form of tumor cell plasticity characterized by reversible adaptive plasticity in murine and human neuroblastoma. Two cellular phenotypes were defined by their ability to exhibit adhered, anchorage dependent (AD) or sphere forming, anchorage independent (AI) growth. The tumor cells could transition back and forth between the two phenotypes and the transition was dependent on the culture conditions. Both cell phenotypes exhibited stem-like features such as expression of nestin, self-renewal capacity, and mesenchymal differentiation potential. The AI tumorspheres were found to be more resistant to chemotherapy and proliferated slower in vitro compared to the AD cells. Identification of specific molecular markers like MAP2, β-catenin, and PDGFRβ enabled us to characterize and observe both phenotypes in established mouse tumors. Irrespective of the phenotype originally implanted in mice, tumors grown in vivo show phenotypic heterogeneity in molecular marker signatures and are indistinguishable in growth or histologic appearance. Similar molecular marker heterogeneity was demonstrated in primary human tumor specimens. Chemotherapy or growth factor receptor inhibition slowed tumor growth in mice and promoted initial loss of AD or AI heterogeneity, respectively. Simultaneous targeting of both phenotypes led to further tumor growth delay with emergence of new unique phenotypes. Our results demonstrate that neuroblastoma cells are plastic, dynamic, and may optimize their ability to survive by changing their phenotype. Phenotypic switching appears to be an adaptive mechanism to unfavorable selection pressure and could explain the phenotypic and functional heterogeneity of neuroblastoma. en_US
dc.language.iso en en_US
dc.title Reversible adaptive plasticity en_US
dc.type Article en_US
dc.description.version Published en_US
dc.title.subtitle a mechanism for neuroblastoma cell heterogeneity and chemo-resistance en_US
dc.author.school SOP en_US
dc.author.idnumber 201005279 en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Frontiers Oncology en_US
dc.journal.volume 2 en_US
dc.article.pages 82 en_US
dc.identifier.doi http://dx.doi.org/10.3389/fonc.2012.00082 en_US
dc.identifier.ctation Chakrabarti, Lina, Thamara Abou-Antoun, Stanislav Vukmanovic, and Anthony D. Sandler. "Reversible adaptive plasticity: a mechanism for neuroblastoma cell heterogeneity and chemo-resistance." Frontiers in oncology 2 (2012): 82. en_US
dc.author.email tamara.abouantoun@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url http://journal.frontiersin.org/article/10.3389/fonc.2012.00082/full en_US

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