96811 20251127152544.0 doi 10.1186/s12885-019-5883-y sideral 113165 ART-2019-113165 eng Martín-Pardillos, A. Universidad de Zaragoza The role of clonal communication and heterogeneity in breast cancer 2019 Access copy available to the general public Unrestricted 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. info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 3.15 2019 ONCOLOGY 129 / 244 = 0.529 2019 Q3 T2 1.186 2019 Cancer Research 2019 Q2 Oncology 2019 Q2 Genetics 2019 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Chiva, A.V. Vargas, G.B. Blanco, P.H. Cid, R.P. Guijarro, P.J. Hummer, S. Bejar Serrano, E. Rodríguez-Casanova, A. Díaz-Lagares, A. Castellvi, J. Miravet-Verde, S. Serrano, L. Lluch-Senar, M. Sebastian, V. Universidad de Zaragoza (orcid)0000-0002-6873-5244 Bribian, A. Lopez-Mascaraque, L. Lopez-Lopez, R. Cajal, S.R.Y. 5005 555 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Ingeniería Química 19 (2019), 666 [26 pp] BMC CANCER BMC CANCER 1471-2407 3857210 http://zaguan.unizar.es/record/96811/files/texto_completo.pdf Versión publicada 45803 http://zaguan.unizar.es/record/96811/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:96811 articulos driver 2025-11-27-15:23:38 ARTICLE