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dc.contributor.author
Castro Guijarro, Ana Carla
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Vanderhoeven, Fiorella
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Mondaca, Joselina Magali
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Fernandez Muñoz, Juan Manuel
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Redondo, Analía
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Sanchez, Angel Matias
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Flamini, Marina Ines
dc.date.available
2023-01-27T15:30:14Z
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2021
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Combination treatment of retinoic acid plus FAK inhibitor prevents tumor growth and breast cancer cells metastasis; 2nd International Workshop on Translational Cancer Research; Palma de Mallorca; España; 2021; 23-23
dc.identifier.uri
http://hdl.handle.net/11336/185945
dc.description.abstract
Background: All-trans retinoic acid (RA) and its natural and synthetic derivatives, known as retinoids, are promising agents in the treatment and chemoprevention of different neoplasias including breast cancer (BC). Focal adhesion kinase (FAK) is a key regulator of cell motility and its overexpression has been associated to a metastatic behavior of tumors. Thus, pharmaceutical FAK inhibitors (FAKi) have been developed to counter this action. In this work, we evaluated the effect of RA+FAKi combination in tumor progression.Methodology: the murine mammary adenocarcinoma cell line LM3 was used. MTT, pharmacological interaction analysis, western blot, immunofluorescence, adhesion, and migration assays were performed. The orthotopic tumor growth and lung metastasis assay were achieved. To bioinformatics analysis we used the publicly Gene Expression Omnibus database. Results: Bioinformatic data show that the expression of RARA, SRC, PTK2 (FAK) is high, meanwhile RARB and RARG are underexpressed in BC cells. We reveal that in metastatic BC cells, genes encoding proteins that are directly or indirectly modulated by FAK, are deregulated in comparison with normal cells. We showed a different pattern of genes up/down-regulated between RA-resistant and RA-sensitive BC cells. Additionally, we demonstrated that although RA and FAKi administered separately decrease cell viability, adhesion and migration in LM3 cells, their combination exerts a higher effect. In an orthotopic assay of LM3 tumor growth, RA and FAKi separately reduce tumor growth however the combined treatment induced the stronger inhibition. Furthermore, the combination increase mice survival. In an experimental metastatic assay, RA significantly reduced lung metastatic dissemination.Discussion: These results suggested that RA resistance would reflect a deregulation of most of the RA-target genes involved in cell adhesion, migration and invasion. RA+FAKi improves reducing tumor growth and metastasis increasing mice survival. This suggest that the sensibility to RA therapy could be exacerbated with FAKi coadministration in BC tumors.
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application/pdf
dc.language.iso
eng
dc.publisher
Fundació Institut d'Investigació Sanitària Illes Balears
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
RETINOIC ACID
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FAK INHIBITORS
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BREAST CANCER
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CELL MOTILITY
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Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
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Combination treatment of retinoic acid plus FAK inhibitor prevents tumor growth and breast cancer cells metastasis
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info:eu-repo/semantics/publishedVersion
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info:eu-repo/semantics/conferenceObject
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info:ar-repo/semantics/documento de conferencia
dc.date.updated
2022-12-12T23:43:53Z
dc.journal.pagination
23-23
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España
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Palma de Mallorca
dc.description.fil
Fil: Castro Guijarro, Ana Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
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Fil: Vanderhoeven, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
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Fil: Mondaca, Joselina Magali. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
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Fil: Fernandez Muñoz, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
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Fil: Redondo, Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
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Fil: Sanchez, Angel Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
dc.description.fil
Fil: Flamini, Marina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
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dc.coverage
Internacional
dc.type.subtype
Workshop
dc.description.nombreEvento
2nd International Workshop on Translational Cancer Research
dc.date.evento
2021-10-21
dc.description.ciudadEvento
Palma de Mallorca
dc.description.paisEvento
España
dc.type.publicacion
Book
dc.description.institucionOrganizadora
Fundació Institut d'Investigació Sanitària Illes Balears
dc.source.libro
2nd International Workshop on Translational Cancer Research
dc.date.eventoHasta
2021-10-22
dc.type
Workshop
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