A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integration
This thesis aims to fill gaps in the research on breast microvasculature by creating a perfusable microvasculature system within a microfluidic platform. For the first time, we co-cultured primary breast endothelial cells and fibroblasts to establish mammary-specific microvessels. Using this system,...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/694422 |
| Acceso en línea: | http://hdl.handle.net/10803/694422 |
| Access Level: | acceso abierto |
| Palabra clave: | Mammary gland Microvasculature Sex hormones Breast cancer Microfluidic technology Glándula mamaria Microvasculatura Hormonas sexuales Cáncer de mama Tecnología microfluídica 576 |
| id |
ES_b95bc1fa114ff9bafa8bd47ea399df6e |
|---|---|
| oai_identifier_str |
oai:www.tdx.cat:10803/694422 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integrationMoccia, CarmenMammary glandMicrovasculatureSex hormonesBreast cancerMicrofluidic technologyGlándula mamariaMicrovasculaturaHormonas sexualesCáncer de mamaTecnología microfluídica576This thesis aims to fill gaps in the research on breast microvasculature by creating a perfusable microvasculature system within a microfluidic platform. For the first time, we co-cultured primary breast endothelial cells and fibroblasts to establish mammary-specific microvessels. Using this system, the two main aims are to explore dose-dependent responses of breast microvasculature to sex hormones and integrate luminal-like breast cancer. To achieve the first objective, we simulate different phases of the menstrual cycle by combining varying concentrations of estrogen and progesterone. The evaluation encompasses vascular remodeling, barrier function, and the release of angiogenic factors within the mammary microvasculature. Tissue specificity is ensured by comparing the breast-specific microvasculature with an alternative model using endothelial cells from a different source and breast fibroblasts. In the second aim, a mammary epithelial layer is integrated, mimicking a lactiferous duct. This setup enables us to investigate the barrier properties of the mammary duct, including the influence of hormonal fluctuations and the effects of tamoxifen. Ultimately, luminal-like breast cancer is incorporated into the system alongside the epithelial mammary layer, simulating ductal carcinoma. This addition contributes to a distinctive 3D model and enhances our comprehension of drug delivery dynamics.Esta tesis tiene como objetivo la investigación sobre la microvasculatura mamaria mediante la creación de un sistema de microvasculatura perfusable utilizando una plataforma microfluídica. Por primera vez, co-cultivamos células endoteliales mamarias primarias y fibroblastos para establecer microvasos específicos de la glándula mamaria. Utilizando este sistema, los dos objetivos principales son explorar las respuestas a diferentes dosis de hormones sexuales la microvasculatura mamaria e integrar un cáncer de mama luminal. Para alcanzar el primer objetivo, simulamos diferentes fases del ciclo menstrual combinando concentraciones variables de estrógeno y progesterona. La evaluación abarca la remodelación vascular, la función de barrera y la liberación de factores angiogénicos dentro de la microvasculatura mamaria. Al comparar la microvasculatura de nuestro sistema con un modelo alternativo de células endoteliales de vena umbilical humana (HUVEC) y fibroblastos de mama, observamos que los efectos hormonales son específicos de la microvasculatura mamaria. En el segundo objetivo, se integra un layer epitelial mamario, imitando un conducto lactífero. Esta configuración nos permite investigar las propiedades de barrera del conducto mamario, incluyendo la influencia de las fluctuaciones hormonales y los efectos del tamoxifeno. Finalmente, se introduce un cáncer de mama luminal en el sistema junto a el layer epitelial mamario, simulando un carcinoma ductal. Esta adición contribuye a un modelo 3D distintivo y mejora nuestra comprensión de la dinámica de la entrega de fármacos.Programa de Doctorat en BiomedicinaUniversitat Pompeu FabraHaase, Kristina MichelleUniversitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida202520252024info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion151 p.application/pdfhttp://hdl.handle.net/10803/694422TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6944222026-06-14T12:46:07Z |
| dc.title.none.fl_str_mv |
A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integration |
| title |
A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integration |
| spellingShingle |
A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integration Moccia, Carmen Mammary gland Microvasculature Sex hormones Breast cancer Microfluidic technology Glándula mamaria Microvasculatura Hormonas sexuales Cáncer de mama Tecnología microfluídica 576 |
| title_short |
A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integration |
| title_full |
A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integration |
| title_fullStr |
A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integration |
| title_full_unstemmed |
A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integration |
| title_sort |
A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integration |
| dc.creator.none.fl_str_mv |
Moccia, Carmen |
| author |
Moccia, Carmen |
| author_facet |
Moccia, Carmen |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
Haase, Kristina Michelle Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida |
| dc.subject.none.fl_str_mv |
Mammary gland Microvasculature Sex hormones Breast cancer Microfluidic technology Glándula mamaria Microvasculatura Hormonas sexuales Cáncer de mama Tecnología microfluídica 576 |
| topic |
Mammary gland Microvasculature Sex hormones Breast cancer Microfluidic technology Glándula mamaria Microvasculatura Hormonas sexuales Cáncer de mama Tecnología microfluídica 576 |
| description |
This thesis aims to fill gaps in the research on breast microvasculature by creating a perfusable microvasculature system within a microfluidic platform. For the first time, we co-cultured primary breast endothelial cells and fibroblasts to establish mammary-specific microvessels. Using this system, the two main aims are to explore dose-dependent responses of breast microvasculature to sex hormones and integrate luminal-like breast cancer. To achieve the first objective, we simulate different phases of the menstrual cycle by combining varying concentrations of estrogen and progesterone. The evaluation encompasses vascular remodeling, barrier function, and the release of angiogenic factors within the mammary microvasculature. Tissue specificity is ensured by comparing the breast-specific microvasculature with an alternative model using endothelial cells from a different source and breast fibroblasts. In the second aim, a mammary epithelial layer is integrated, mimicking a lactiferous duct. This setup enables us to investigate the barrier properties of the mammary duct, including the influence of hormonal fluctuations and the effects of tamoxifen. Ultimately, luminal-like breast cancer is incorporated into the system alongside the epithelial mammary layer, simulating ductal carcinoma. This addition contributes to a distinctive 3D model and enhances our comprehension of drug delivery dynamics. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion |
| format |
doctoralThesis |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10803/694422 |
| url |
http://hdl.handle.net/10803/694422 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
http://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
151 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Universitat Pompeu Fabra |
| publisher.none.fl_str_mv |
Universitat Pompeu Fabra |
| dc.source.none.fl_str_mv |
TDX (Tesis Doctorals en Xarxa) reponame:TDR. Tesis Doctorales en Red instname:CBUC, CESCA |
| instname_str |
CBUC, CESCA |
| reponame_str |
TDR. Tesis Doctorales en Red |
| collection |
TDR. Tesis Doctorales en Red |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869417765905891328 |
| score |
15,812455 |