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

ilustraciones, diagramas

Autores:: Castro Abril, Hector Alfonso

Tipo de recurso:: Doctoral thesis

Fecha de publicación:: 2023

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: eng

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dc.title.eng.fl_str_mv	In vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasis
dc.title.translated.spa.fl_str_mv	Modelado in vitro de los aspectos mecánicos y bioquímicos involucrados en procesos migratorios celulares relacionados con la metástasis de cáncer colorrectal
title	In vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasis
spellingShingle	In vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasis 610 - Medicina y salud::616 - Enfermedades 620 - Ingeniería y operaciones afines Neoplasias Colorrectales Técnicas In Vitro Fenómenos Fisiológicos Celulares Colorectal Neoplasms In Vitro Techniques Cell Physiological Phenomena Cancer Spheroids Migration Invasion Collagen Hydrogels Mechanobiology Cytoskeleton Contraction Colon Cáncer Colon Esferoides Migración Invasión Colágeno Hidrogeles Mecanobiología Citoesqueleto Contracción
title_short	In vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasis
title_full	In vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasis
title_fullStr	In vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasis
title_full_unstemmed	In vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasis
title_sort	In vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasis
dc.creator.fl_str_mv	Castro Abril, Hector Alfonso
dc.contributor.advisor.spa.fl_str_mv	Ochoa Garrido, Ignacio Doblaré Castellano, Manuel Garzón Alvarado, Diego Alexander
dc.contributor.author.spa.fl_str_mv	Castro Abril, Hector Alfonso
dc.contributor.researchgroup.spa.fl_str_mv	laboratorio de Biomiméticos: Grupo de Mecanobiología de Órganos y Tejidos TME Lab (Universidad de Zaragoza)
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud::616 - Enfermedades 620 - Ingeniería y operaciones afines
topic	610 - Medicina y salud::616 - Enfermedades 620 - Ingeniería y operaciones afines Neoplasias Colorrectales Técnicas In Vitro Fenómenos Fisiológicos Celulares Colorectal Neoplasms In Vitro Techniques Cell Physiological Phenomena Cancer Spheroids Migration Invasion Collagen Hydrogels Mechanobiology Cytoskeleton Contraction Colon Cáncer Colon Esferoides Migración Invasión Colágeno Hidrogeles Mecanobiología Citoesqueleto Contracción
dc.subject.decs.spa.fl_str_mv	Neoplasias Colorrectales Técnicas In Vitro Fenómenos Fisiológicos Celulares
dc.subject.decs.eng.fl_str_mv	Colorectal Neoplasms In Vitro Techniques Cell Physiological Phenomena
dc.subject.proposal.eng.fl_str_mv	Cancer Spheroids Migration Invasion Collagen Hydrogels Mechanobiology Cytoskeleton Contraction
dc.subject.proposal.spa.fl_str_mv	Colon Cáncer Colon Esferoides Migración Invasión Colágeno Hidrogeles Mecanobiología Citoesqueleto Contracción
description	ilustraciones, diagramas
publishDate	2023
dc.date.issued.none.fl_str_mv	2023-12
dc.date.accessioned.none.fl_str_mv	2024-03-12T19:07:21Z
dc.date.available.none.fl_str_mv	2024-03-12T19:07:21Z
dc.type.spa.fl_str_mv	Trabajo de grado - Doctorado
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/doctoralThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.coar.spa.fl_str_mv	http://purl.org/coar/resource_type/c_db06
dc.type.content.spa.fl_str_mv	Text
dc.type.redcol.spa.fl_str_mv	http://purl.org/redcol/resource_type/TD
format	http://purl.org/coar/resource_type/c_db06
status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	https://repositorio.unal.edu.co/handle/unal/85800
dc.identifier.instname.spa.fl_str_mv	Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv	https://repositorio.unal.edu.co/
url	https://repositorio.unal.edu.co/handle/unal/85800 https://repositorio.unal.edu.co/
identifier_str_mv	Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv	eng
language	eng
dc.relation.indexed.spa.fl_str_mv	Bireme
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spelling	Atribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Ochoa Garrido, Ignacioc49869d52d504ae49ddce0be875b1253Doblaré Castellano, Manuel6fde4f6757f4005b690ee1f187a56551Garzón Alvarado, Diego Alexandera780fc0a2dd14ac611c37bca9998c94bCastro Abril, Hector Alfonso0f96e65bd8b2187f6f76900025fde6f7laboratorio de Biomiméticos: Grupo de Mecanobiología de Órganos y TejidosTME Lab (Universidad de Zaragoza)2024-03-12T19:07:21Z2024-03-12T19:07:21Z2023-12https://repositorio.unal.edu.co/handle/unal/85800Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramasMetastasis 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.La 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).Colciencias - Convocatoria 785 de Doctorados NacionalesTesis de doble titulación con la Universidad de ZaragozaDoctoradoDoctor en Ingenieríaxxvi, 198 páginasapplication/pdfengUniversidad Nacional de ColombiaBogotá - Ingeniería - Doctorado en Ingeniería - Ingeniería Mecánica y MecatrónicaFacultad de IngenieríaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::616 - Enfermedades620 - Ingeniería y operaciones afinesNeoplasias ColorrectalesTécnicas In VitroFenómenos Fisiológicos CelularesColorectal NeoplasmsIn Vitro TechniquesCell Physiological PhenomenaCancerSpheroidsMigrationInvasionCollagenHydrogelsMechanobiologyCytoskeletonContractionColonCáncerColonEsferoidesMigraciónInvasiónColágenoHidrogelesMecanobiologíaCitoesqueletoContracciónIn vitro modeling of mechanical and biochemical aspects involved in the cellular migratory processes related with colorectal cancer metastasisModelado in vitro de los aspectos mecánicos y bioquímicos involucrados en procesos migratorios celulares relacionados con la metástasis de cáncer colorrectalTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttp://purl.org/redcol/resource_type/TDBiremeAbedin, Monika, and Nicole King. 2010. “Diverse Evolutionary Paths to Cell Adhesion.” Trends in Cell Biology 20 (December): 734–42. https://doi.org/10.1016/j.tcb.2010.08.002.Acharya, B. 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Allen. 1997. “A three-dimensional finite element formulation for thermoviscoelastic orthotropic media.” International Journal for Numerical Methods in Engineering. https://doi.org/10.1002/(SICI)1097- 0207(19970630)40:12<2267::AID-NME156>3.0.CO;2-PEstudiantesInvestigadoresPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/85800/3/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD53ORIGINAL1070948613.2023.pdf1070948613.2023.pdfTesis de Doctorado en Ingeniería - Ingeniería Mecánica y Mecatrónicaapplication/pdf97810562https://repositorio.unal.edu.co/bitstream/unal/85800/4/1070948613.2023.pdfc1b6d23537713936b798da0b582ff547MD54THUMBNAIL1070948613.2023.pdf.jpg1070948613.2023.pdf.jpgGenerated Thumbnailimage/jpeg6144https://repositorio.unal.edu.co/bitstream/unal/85800/5/1070948613.2023.pdf.jpg18e1fb0484dd6a7859eab5653646de3eMD55unal/85800oai:repositorio.unal.edu.co:unal/858002024-08-23 23:10:39.981Repositorio Institucional 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