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 documento: | artigo |
| Data de publicação: | 2019 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositório: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/185584 |
| Acesso em linha: | http://hdl.handle.net/10261/185584 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Tumor Breast Cancer Metastasis Heterogeneity Clone Communication Cooperation MDA-MB-231 |
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oai:digital.csic.es:10261/185584 |
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The role of clonal communication and heterogeneity in breast cancerMartín-Pardillos, AnaValls Chiva, ÁngelesBande Vargas, GemmaHurtado Blanco, PabloPiñeiro Cid, RobertoGuijarro, Pedro J.Hümmer, StefanBejar Serrano, EvaRodriguez-Casanova, AitorDíaz-Lagares, ÁngelCastellví, JosepMiravet-Verde, SamuelSerrano, LuisLluch-Senar, MaríaSebastián, VíctorBribián, AnaLópez-Mascaraque, LauraLópez-López, RafaelRamón y Cajal, SantiagoTumorBreastCancerMetastasisHeterogeneityCloneCommunicationCooperationMDA-MB-231[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.SRYC acknowledges support from Fondo de Investigaciones Sanitarias (FIS; PI17/02247 and PI14/01320), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC; CB16/12/00363) and Generalitat de Catalunya (AGAUR; 2017 SGR 1799 and 2014 SGR 1131). AMP is funded by a FP7 Marie Sklodowska-Curie COFUND program under Grant Agreement n° 267128 (INCOMED program). ADL is funded by a “Juan Rodés” contract (JR17/00016) from ISCIII.Peer reviewedBioMed CentralGeneralitat de CatalunyaInstituto de Salud Carlos IIIEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2019201920192019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/185584reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/FP7/267128https://doi.org/10.1186/s12885-019-5883-yPublisher's versionSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1855842026-05-22T06:33:51Z |
| 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, Ana 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, Ana Valls Chiva, Ángeles Bande Vargas, Gemma Hurtado Blanco, Pablo Piñeiro Cid, Roberto Guijarro, Pedro J. Hümmer, Stefan Bejar Serrano, Eva Rodriguez-Casanova, Aitor Díaz-Lagares, Ángel Castellví, Josep Miravet-Verde, Samuel Serrano, Luis Lluch-Senar, María Sebastián, Víctor Bribián, Ana López-Mascaraque, Laura López-López, Rafael Ramón y Cajal, Santiago |
| author |
Martín-Pardillos, Ana |
| author_facet |
Martín-Pardillos, Ana Valls Chiva, Ángeles Bande Vargas, Gemma Hurtado Blanco, Pablo Piñeiro Cid, Roberto Guijarro, Pedro J. Hümmer, Stefan Bejar Serrano, Eva Rodriguez-Casanova, Aitor Díaz-Lagares, Ángel Castellví, Josep Miravet-Verde, Samuel Serrano, Luis Lluch-Senar, María Sebastián, Víctor Bribián, Ana López-Mascaraque, Laura López-López, Rafael Ramón y Cajal, Santiago |
| author_role |
author |
| author2 |
Valls Chiva, Ángeles Bande Vargas, Gemma Hurtado Blanco, Pablo Piñeiro Cid, Roberto Guijarro, Pedro J. Hümmer, Stefan Bejar Serrano, Eva Rodriguez-Casanova, Aitor Díaz-Lagares, Ángel Castellví, Josep Miravet-Verde, Samuel Serrano, Luis Lluch-Senar, María Sebastián, Víctor Bribián, Ana López-Mascaraque, Laura López-López, Rafael Ramón y Cajal, Santiago |
| 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 |
Generalitat de Catalunya Instituto de Salud Carlos III European Commission Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| 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. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019 2019 2019 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/185584 |
| url |
http://hdl.handle.net/10261/185584 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
#PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/EC/FP7/267128 https://doi.org/10.1186/s12885-019-5883-y Publisher's version Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
BioMed Central |
| publisher.none.fl_str_mv |
BioMed Central |
| dc.source.none.fl_str_mv |
reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
| instname_str |
Consejo Superior de Investigaciones Científicas (CSIC) |
| reponame_str |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
| collection |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
| repository.name.fl_str_mv |
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1869419612330786816 |
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15,812429 |