The role of clonal communication and heterogeneity in breast cancer
Background: Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in molecular and phenotypic heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells. We...
| Autores: | , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:223814 |
| Acceso en línea: | https://ddd.uab.cat/record/223814 https://dx.doi.org/urn:doi:10.1186/s12885-019-5883-y |
| Access Level: | acceso abierto |
| Palabra clave: | Tumor Breast Cancer Metastasis Heterogeneity Clone Communication Cooperation MDA-MB-231 |
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The role of clonal communication and heterogeneity in breast cancerMartín-Pardillos, A.|||0000-0003-1717-8465Valls Chiva, Á.Bande Vargas, G.Hurtado Blanco, P.Piñeiro Cid, R.Guijarro, Pedro J.Hümmer, Stefan|||0000-0002-8184-3872Bejar Serrano, Eva|||0000-0002-1843-3010Rodriguez-Casanova, A.Diaz-Lagares, Angel|||0000-0002-9114-9227Castellvi, Josep|||0000-0001-5745-9996Miravet-Verde, S.Serrano, L.Lluch-Senar, M.Sebastian, V.Bribian, A.López-Mascaraque, L.López-López, R.Ramón y Cajal, S.TumorBreastCancerMetastasisHeterogeneityCloneCommunicationCooperationMDA-MB-231Background: Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in molecular and phenotypic heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells. We aimed to dissect the molecular mechanisms underlying the cooperation between different clones. Methods: We produced clonal cell lines derived from the MDA-MB-231 breast cancer cell line, using the UbC-StarTrack system, which allowed tracking of multiple clones by color: GFP C3, mKO E10 and Sapphire D7. Characterization of these clones was performed by growth rate, cell metabolic activity, wound healing, invasion assays and genetic and epigenetic arrays. Tumorigenicity was tested by orthotopic and intravenous injections. Clonal cooperation was evaluated by medium complementation, co-culture and co-injection assays. Results: Characterization of these clones in vitro revealed clear genetic and epigenetic differences that affected growth rate, cell metabolic activity, morphology and cytokine expression among cell lines. In vivo, all clonal cell lines were able to form tumors; however, injection of an equal mix of the different clones led to tumors with very few mKO E10 cells. Additionally, the mKO E10 clonal cell line showed a significant inability to form lung metastases. These results confirm that even in stable cell lines heterogeneity is present. In vitro, the complementation of growth medium with medium or exosomes from parental or clonal cell lines increased the growth rate of the other clones. Complementation assays, co-growth and co-injection of mKO E10 and GFP C3 clonal cell lines increased the efficiency of invasion and migration. Conclusions: These findings support a model where interplay between clones confers aggressiveness, and which may allow identification of the factors involved in cellular communication that could play a role in clonal cooperation and thus represent new targets for preventing tumor progression.Universitat Autònoma de Barcelona 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/223814https://dx.doi.org/urn:doi:10.1186/s12885-019-5883-yreponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/02247Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/01320Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-1799Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-1131open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2238142026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
The role of clonal communication and heterogeneity in breast cancer |
| title |
The role of clonal communication and heterogeneity in breast cancer |
| spellingShingle |
The role of clonal communication and heterogeneity in breast cancer Martín-Pardillos, A.|||0000-0003-1717-8465 Tumor Breast Cancer Metastasis Heterogeneity Clone Communication Cooperation MDA-MB-231 |
| title_short |
The role of clonal communication and heterogeneity in breast cancer |
| title_full |
The role of clonal communication and heterogeneity in breast cancer |
| title_fullStr |
The role of clonal communication and heterogeneity in breast cancer |
| title_full_unstemmed |
The role of clonal communication and heterogeneity in breast cancer |
| title_sort |
The role of clonal communication and heterogeneity in breast cancer |
| dc.creator.none.fl_str_mv |
Martín-Pardillos, A.|||0000-0003-1717-8465 Valls Chiva, Á. Bande Vargas, G. Hurtado Blanco, P. Piñeiro Cid, R. Guijarro, Pedro J. Hümmer, Stefan|||0000-0002-8184-3872 Bejar Serrano, Eva|||0000-0002-1843-3010 Rodriguez-Casanova, A. Diaz-Lagares, Angel|||0000-0002-9114-9227 Castellvi, Josep|||0000-0001-5745-9996 Miravet-Verde, S. Serrano, L. Lluch-Senar, M. Sebastian, V. Bribian, A. López-Mascaraque, L. López-López, R. Ramón y Cajal, S. |
| author |
Martín-Pardillos, A.|||0000-0003-1717-8465 |
| author_facet |
Martín-Pardillos, A.|||0000-0003-1717-8465 Valls Chiva, Á. Bande Vargas, G. Hurtado Blanco, P. Piñeiro Cid, R. Guijarro, Pedro J. Hümmer, Stefan|||0000-0002-8184-3872 Bejar Serrano, Eva|||0000-0002-1843-3010 Rodriguez-Casanova, A. Diaz-Lagares, Angel|||0000-0002-9114-9227 Castellvi, Josep|||0000-0001-5745-9996 Miravet-Verde, S. Serrano, L. Lluch-Senar, M. Sebastian, V. Bribian, A. López-Mascaraque, L. López-López, R. Ramón y Cajal, S. |
| author_role |
author |
| author2 |
Valls Chiva, Á. Bande Vargas, G. Hurtado Blanco, P. Piñeiro Cid, R. Guijarro, Pedro J. Hümmer, Stefan|||0000-0002-8184-3872 Bejar Serrano, Eva|||0000-0002-1843-3010 Rodriguez-Casanova, A. Diaz-Lagares, Angel|||0000-0002-9114-9227 Castellvi, Josep|||0000-0001-5745-9996 Miravet-Verde, S. Serrano, L. Lluch-Senar, M. Sebastian, V. Bribian, A. López-Mascaraque, L. López-López, R. Ramón y Cajal, S. |
| author2_role |
author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Tumor Breast Cancer Metastasis Heterogeneity Clone Communication Cooperation MDA-MB-231 |
| topic |
Tumor Breast Cancer Metastasis Heterogeneity Clone Communication Cooperation MDA-MB-231 |
| description |
Background: Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in molecular and phenotypic heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells. We aimed to dissect the molecular mechanisms underlying the cooperation between different clones. Methods: We produced clonal cell lines derived from the MDA-MB-231 breast cancer cell line, using the UbC-StarTrack system, which allowed tracking of multiple clones by color: GFP C3, mKO E10 and Sapphire D7. Characterization of these clones was performed by growth rate, cell metabolic activity, wound healing, invasion assays and genetic and epigenetic arrays. Tumorigenicity was tested by orthotopic and intravenous injections. Clonal cooperation was evaluated by medium complementation, co-culture and co-injection assays. Results: Characterization of these clones in vitro revealed clear genetic and epigenetic differences that affected growth rate, cell metabolic activity, morphology and cytokine expression among cell lines. In vivo, all clonal cell lines were able to form tumors; however, injection of an equal mix of the different clones led to tumors with very few mKO E10 cells. Additionally, the mKO E10 clonal cell line showed a significant inability to form lung metastases. These results confirm that even in stable cell lines heterogeneity is present. In vitro, the complementation of growth medium with medium or exosomes from parental or clonal cell lines increased the growth rate of the other clones. Complementation assays, co-growth and co-injection of mKO E10 and GFP C3 clonal cell lines increased the efficiency of invasion and migration. Conclusions: These findings support a model where interplay between clones confers aggressiveness, and which may allow identification of the factors involved in cellular communication that could play a role in clonal cooperation and thus represent new targets for preventing tumor progression. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2 2019-01-01 2019 2019-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/223814 https://dx.doi.org/urn:doi:10.1186/s12885-019-5883-y |
| url |
https://ddd.uab.cat/record/223814 https://dx.doi.org/urn:doi:10.1186/s12885-019-5883-y |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17/02247 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI14/01320 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-1799 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-1131 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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