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In vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasis

dc.rights.licenseAtribución-NoComercial 4.0 Internacional
dc.contributor.advisorOchoa Garrido, Ignacio
dc.contributor.advisorDoblaré Castellano, Manuel
dc.contributor.advisorGarzón Alvarado, Diego Alexander
dc.contributor.authorCastro Abril, Hector Alfonso
dc.date.accessioned2024-03-12T19:07:21Z
dc.date.available2024-03-12T19:07:21Z
dc.date.issued2023-12
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/85800
dc.descriptionilustraciones, diagramas
dc.description.abstractMetastasis is one of the most lethal manifestations in cancer, accounting for up to 90% of cancer related deaths. Recently, it has been shown that the mechanics of tissues, as well as the biological response of cells to different biophysical stimuli, play an active role in the development of cancer as well as in metastasis. Since this disease is a major concern in public health, understanding the biology of metastasis and how mechanics affect this process is essential to develop new therapeutic strategies to attack and even prevent it. The main aim of this thesis was to study the role of the mechanical environment and the nutrient availability in the evolution of Colorectal Cancer (CRC), one of the leading causes of cancer deaths worldwide. For this, we first varied different fabrication parameters of previously established pro tocols for generating type I collagen hydrogels. With these hydrogels, we studied the migrating behavior of CRC cell-line spheroids and found that the combined effect of the ultrastructure of the hydrogels and their mechanical stiffness generated profound distinct patterns in cell invasion. In a parallel approach, we analyzed the response of spheroids to dynamic changes in glucose and Fetal Bovine Serum (FBS) availability in order to check whether these changes generated an adaptive response in the samples. Our results showed that the spheroids indeed had the ability to adapt to nutrient-deprived environments, especially after several cycles of nutrient-abundance and nutrient-starvation. Furthermore, in the case of the HCT-116 cell line, we observed that the spheroids expelled their necrotic core during the starvation cycles, a striking phenomenon that, to the best of our knowledge, has never been reported in literature. Due to the notoriety of the event, we explored, in the last part of this thesis, the possible mech anisms involved in the ejection of the core. For this, we explored different cytoskeleton (CSK) blockers in the preconditioned spheroids during the starvation periods to check whether the ejec tion of the core was related to cell contraction. This approach allowed us to conclude that it was indeed involved in the phenomenon, since blocked spheroids did not eject their core during the mentioned period.
dc.description.abstractLa metástasis es una de las manifestaciones más letales del cáncer, con un estimado de 90% de muertes relacionadas por cáncer. Recientemente, se ha demostrado que la mecánica de los tejidos y la respuesta biológica de las células ante distintos estímulos biofísicos juegan un papel activo en el desarrollo del cáncer y la metástasis. Dado que esta enfermedad es un problema de salud pública, el entendimiento de la biología de la metástasis y la forma en la que la mecánica afecta este proceso es esencial para desarrollar nuevas estrategias terapéuticas para atacarla e incluso prevenirla. El objetivo principal de esta tesis consistió en estudiar el rol del entorno mecánico y la disponibilidad de nutrientes en la evolución del cáncer colorrectal (CRC por sus siglas en inglés), una de las principales causas de muerte por cáncer en el mundo. Para esto, se variaron diferentes parámetros de fabricación de hidrogeles de colágeno tipo I previamente descritos en literatura. Con estos hidrogeles, se estudió el comportamiento migratorio de esferoides celulares derivados de líneas celulares de CRC y se encontró que el efecto combinado de la ultraestructura de los hidrogeles y de su rigidez mecánica generaban patrones invasivos profundamente distintos. En una aproximación paralela, se analizó la respuesta de los esferoides ante cambios dinámicos en la disponibilidad de glucosa o suero fetal bovino (FBS, por sus siglas en inglés) con el fin de estudiar la potencial respuesta adaptativa de las muestras ante dichas variaciones. Los resultados demostraron que los esferoides efectivamente tenían la habilidad de adaptarse a entornos privados de nutrientes, especialmente después de varios ciclos de abundancia e inanición. De manera adicional, se observó que, en el caso de la línea celular HCT-116, los esferoides expulsaron su núcleo necrótico durante los ciclos de deprivación, un fenómeno que, en lo que a los autores concierne, nunca ha sido reportado en literatura. Debido a la notoriedad de este evento se exploró, en la última parte de esta tesis, los mecanismos posiblemente involucrados en la eyección del núcleo. Para esto, se exploraron diferentes bloqueadores del citoesqueleto en esferoides durante los períodos de inanición para comprobar la relación entre la expulsión y la contracción celular. Este enfoque permitió concluir que efectivamente había un vínculo, pues los esferoides tratados no eyectaron su núcleo durante los ciclos mencionados. (Texto tomado de la fuente).
dc.description.sponsorshipColciencias - Convocatoria 785 de Doctorados Nacionales
dc.format.extentxxvi, 198 páginas
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherUniversidad Nacional de Colombia
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subject.ddc610 - Medicina y salud::616 - Enfermedades
dc.subject.ddc620 - Ingeniería y operaciones afines
dc.titleIn vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasis
dc.typeTrabajo de grado - Doctorado
dc.type.driverinfo:eu-repo/semantics/doctoralThesis
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.publisher.programBogotá - Ingeniería - Doctorado en Ingeniería - Ingeniería Mecánica y Mecatrónica
dc.description.notesTesis de doble titulación con la Universidad de Zaragoza
dc.contributor.researchgrouplaboratorio de Biomiméticos: Grupo de Mecanobiología de Órganos y Tejidos
dc.contributor.researchgroupTME Lab (Universidad de Zaragoza)
dc.description.degreelevelDoctorado
dc.description.degreenameDoctor en Ingeniería
dc.identifier.instnameUniversidad Nacional de Colombia
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourlhttps://repositorio.unal.edu.co/
dc.publisher.facultyFacultad de Ingeniería
dc.publisher.placeBogotá, Colombia
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
dc.relation.indexedBireme
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.subject.decsNeoplasias Colorrectales
dc.subject.decsColorectal Neoplasms
dc.subject.decsTécnicas In Vitro
dc.subject.decsIn Vitro Techniques
dc.subject.decsFenómenos Fisiológicos Celulares
dc.subject.decsCell Physiological Phenomena
dc.subject.proposalCancer
dc.subject.proposalColon
dc.subject.proposalSpheroids
dc.subject.proposalMigration
dc.subject.proposalInvasion
dc.subject.proposalCollagen
dc.subject.proposalHydrogels
dc.subject.proposalMechanobiology
dc.subject.proposalCytoskeleton
dc.subject.proposalContraction
dc.subject.proposalCáncer
dc.subject.proposalColon
dc.subject.proposalEsferoides
dc.subject.proposalMigración
dc.subject.proposalInvasión
dc.subject.proposalColágeno
dc.subject.proposalHidrogeles
dc.subject.proposalMecanobiología
dc.subject.proposalCitoesqueleto
dc.subject.proposalContracción
dc.title.translatedModelado in vitro de los aspectos mecánicos y bioquímicos involucrados en procesos migratorios celulares relacionados con la metástasis de cáncer colorrectal
dc.type.coarhttp://purl.org/coar/resource_type/c_db06
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
dc.type.redcolhttp://purl.org/redcol/resource_type/TD
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2
dcterms.audience.professionaldevelopmentEstudiantes
dcterms.audience.professionaldevelopmentInvestigadores
dcterms.audience.professionaldevelopmentPúblico general


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