Obesity and melanoma metastasis: Understanding the relevance of the adipose tissue as pre-metastatic niche in melanoma

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 20-04-2021

Detalles Bibliográficos
Autor: Robado de Lope, Lucía
Tipo de recurso: tesis doctoral
Fecha de publicación:2021
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/696361
Acceso en línea:http://hdl.handle.net/10486/696361
Access Level:acceso abierto
Palabra clave:Cáncer - Obesidad - Tesis doctorales
Metástasis de melanoma - Obesidad - Tesis doctorales
Biología y Biomedicina / Biología
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spelling Obesity and melanoma metastasis: Understanding the relevance of the adipose tissue as pre-metastatic niche in melanomaObesidad y melanoma metástasis: estudio de la importancia del tejido adiposo como nicho pre-metastático en melanomaRobado de Lope, LucíaCáncer - Obesidad - Tesis doctoralesMetástasis de melanoma - Obesidad - Tesis doctoralesBiología y Biomedicina / BiologíaTesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 20-04-2021Esta tesis tiene embargado el acceso al texto completo hasta el 20-10-2022Increasing evidence support a link between obesity and tumor progression of various types of cancer. In melanoma, although controversial, studies in murine models and epidemiological data point to a positive correlation between obesity and melanoma incidence and progression. However, the implication of obesity in metastasis and the mechanisms underlying this association remain largely unexplored. Tumor microenvironment and pre-metastatic niche formation are two key processes governing metastasis. In this sense, in this thesis we tried to shed light on the underlying mechanisms linking obesity and melanoma metastasis, focusing on the study of the generation of novel pre-metastatic niches in the obese adipose tissue that we named “obese niches”. Here we show that HFD increases metastasis of the low metastatic B16-F1 melanoma model in retroperitoneal, epidydimal and inguinal fat tissue while this influence was not observed using the high metastatic B16-F10 model. Analysis of the factors involved shows that HFD induces the hypersecretion of different molecules in the retroperitoneal adipose tissue such as CCL6 that could be involved in melanoma metastasis. However, the analysis of CCL6 revealed that it does not have a direct role attracting melanoma cells. Our data support instead, that it may have an indirect role contributing to macrophage recruitment altering the tumor microenvironment. We observed an increased recruitment of macrophages in the adipose tissue of HFD-fed mice with expression of genes associated with an M2 phenotype such as Il10, Il1rn and Arg1. Finally, co-culture of B16-F1 melanoma cells with adipose tissue from HFD-fed mice, induced the expression of fibronectin and galectin 3 in melanoma cells and alters MAPK and STAT3 signaling pathways. Overall, our data suggest that the adipose tissue from HFD-fed mice favors B16-F1 metastasis and promotes the expression of pro-metastatic and pro-survival genes such as Fn1 or Lgals3. Although the mechanism involved in tumor cells homing to the adipose tissue needs further investigation, the increase secretion of cytokines such as CCL6 suggest the recruitment of M2 macrophages that could induce the formation of novel “obese niches” and favor melanoma metastasisPeinado Selgas, HéctorDepartamento de BioquímicaFacultad de MedicinaCentro Nacional de Investigaciones Oncológicas (CNIO)20212021-04-20doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/696361reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6963612026-06-23T12:46:27Z
dc.title.none.fl_str_mv Obesity and melanoma metastasis: Understanding the relevance of the adipose tissue as pre-metastatic niche in melanoma
Obesidad y melanoma metástasis: estudio de la importancia del tejido adiposo como nicho pre-metastático en melanoma
title Obesity and melanoma metastasis: Understanding the relevance of the adipose tissue as pre-metastatic niche in melanoma
spellingShingle Obesity and melanoma metastasis: Understanding the relevance of the adipose tissue as pre-metastatic niche in melanoma
Robado de Lope, Lucía
Cáncer - Obesidad - Tesis doctorales
Metástasis de melanoma - Obesidad - Tesis doctorales
Biología y Biomedicina / Biología
title_short Obesity and melanoma metastasis: Understanding the relevance of the adipose tissue as pre-metastatic niche in melanoma
title_full Obesity and melanoma metastasis: Understanding the relevance of the adipose tissue as pre-metastatic niche in melanoma
title_fullStr Obesity and melanoma metastasis: Understanding the relevance of the adipose tissue as pre-metastatic niche in melanoma
title_full_unstemmed Obesity and melanoma metastasis: Understanding the relevance of the adipose tissue as pre-metastatic niche in melanoma
title_sort Obesity and melanoma metastasis: Understanding the relevance of the adipose tissue as pre-metastatic niche in melanoma
dc.creator.none.fl_str_mv Robado de Lope, Lucía
author Robado de Lope, Lucía
author_facet Robado de Lope, Lucía
author_role author
dc.contributor.none.fl_str_mv Peinado Selgas, Héctor
Departamento de Bioquímica
Facultad de Medicina
Centro Nacional de Investigaciones Oncológicas (CNIO)
dc.subject.none.fl_str_mv Cáncer - Obesidad - Tesis doctorales
Metástasis de melanoma - Obesidad - Tesis doctorales
Biología y Biomedicina / Biología
topic Cáncer - Obesidad - Tesis doctorales
Metástasis de melanoma - Obesidad - Tesis doctorales
Biología y Biomedicina / Biología
description Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 20-04-2021
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-04-20
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/696361
url http://hdl.handle.net/10486/696361
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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