Reversible adaptive plasticity
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 cell...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , |
| التنسيق: | article |
| منشور في: |
2012
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/4418 http://dx.doi.org/10.3389/fonc.2012.00082 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://journal.frontiersin.org/article/10.3389/fonc.2012.00082/full |
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| _version_ | 1864513463564369920 |
|---|---|
| author | Abou-Antoun, Thamara |
| author2 | Chakrabati, Lina Vykmanovic, Stainslav Sandler, Anthony D. |
| author2_role | author author author |
| author_facet | Abou-Antoun, Thamara Chakrabati, Lina Vykmanovic, Stainslav Sandler, Anthony D. |
| author_role | author |
| dc.creator.none.fl_str_mv | Abou-Antoun, Thamara Chakrabati, Lina Vykmanovic, Stainslav Sandler, Anthony D. |
| dc.date.none.fl_str_mv | 2012 2016-09-27T09:30:11Z 2016-09-27T09:30:11Z 2016-09-27 |
| dc.identifier.none.fl_str_mv | 2234-943X http://hdl.handle.net/10725/4418 http://dx.doi.org/10.3389/fonc.2012.00082 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. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://journal.frontiersin.org/article/10.3389/fonc.2012.00082/full |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Frontiers Oncology |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Reversible adaptive plasticity a mechanism for neuroblastoma cell heterogeneity and chemo-resistance |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_9ff4c033262f4480d19225631b73eb93 |
| identifier_str_mv | 2234-943X 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. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/4418 |
| publishDate | 2012 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Reversible adaptive plasticitya mechanism for neuroblastoma cell heterogeneity and chemo-resistanceAbou-Antoun, ThamaraChakrabati, LinaVykmanovic, StainslavSandler, Anthony D.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.PublishedN/A2016-09-27T09:30:11Z2016-09-27T09:30:11Z20122016-09-27Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2234-943Xhttp://hdl.handle.net/10725/4418http://dx.doi.org/10.3389/fonc.2012.00082Chakrabarti, 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.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttp://journal.frontiersin.org/article/10.3389/fonc.2012.00082/fullenFrontiers Oncologyinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/44182021-03-19T10:00:46Z |
| spellingShingle | Reversible adaptive plasticity Abou-Antoun, Thamara |
| status_str | publishedVersion |
| title | Reversible adaptive plasticity |
| title_full | Reversible adaptive plasticity |
| title_fullStr | Reversible adaptive plasticity |
| title_full_unstemmed | Reversible adaptive plasticity |
| title_short | Reversible adaptive plasticity |
| title_sort | Reversible adaptive plasticity |
| url | http://hdl.handle.net/10725/4418 http://dx.doi.org/10.3389/fonc.2012.00082 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://journal.frontiersin.org/article/10.3389/fonc.2012.00082/full |