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Ascites microenvironment conditions the peritoneal pre-metastatic niche to promote the implantation of ovarian tumor spheroids: Involvement of fibrinogen/fibrin and αV and α5ß1 integrins.
Laurent-Issartel, Carine; Landras, Alexandra; Agniel, Rémy; Giffard, Florence; Blanc-Fournier, Cécile; Da Silva Cruz, Elisabete; Habes, Chahrazed; Leroy-Dudal, Johanne; Carreiras, Franck; Kellouche, Sabrina.
Afiliação
  • Laurent-Issartel C; Equipe de Recherche sur Les Relations Matrice Extracellulaire-Cellules, ERRMECe, (EA1391), Groupe Matrice Extracellulaire et Physiopathologie (MECuP), Institut des Materiaux, I-MAT (FD4122), CY Cergy Paris Université, France.
  • Landras A; Equipe de Recherche sur Les Relations Matrice Extracellulaire-Cellules, ERRMECe, (EA1391), Groupe Matrice Extracellulaire et Physiopathologie (MECuP), Institut des Materiaux, I-MAT (FD4122), CY Cergy Paris Université, France.
  • Agniel R; Equipe de Recherche sur Les Relations Matrice Extracellulaire-Cellules, ERRMECe, (EA1391), Groupe Matrice Extracellulaire et Physiopathologie (MECuP), Institut des Materiaux, I-MAT (FD4122), CY Cergy Paris Université, France.
  • Giffard F; UNICANCER, F. Baclesse Comprehensive Cancer Center, Biopathology Department, Caen, France; Université de Caen Normandie, Inserm U1086 ANTICIPE, Caen, France; Université de Caen Normandie, Unité de Services PLATON, Plateforme Virtual'His, Caen, France.
  • Blanc-Fournier C; UNICANCER, F. Baclesse Comprehensive Cancer Center, Biopathology Department, Caen, France; Université de Caen Normandie, Unité de Services PLATON, Centre de Ressources Biologiques OvaRessources, Caen, France.
  • Da Silva Cruz E; University of Strasbourg, Laboratory of Bioimaging and Pathologies, UMR CNRS 7021, Illkirch, France.
  • Habes C; Equipe de Recherche sur Les Relations Matrice Extracellulaire-Cellules, ERRMECe, (EA1391), Groupe Matrice Extracellulaire et Physiopathologie (MECuP), Institut des Materiaux, I-MAT (FD4122), CY Cergy Paris Université, France.
  • Leroy-Dudal J; Equipe de Recherche sur Les Relations Matrice Extracellulaire-Cellules, ERRMECe, (EA1391), Groupe Matrice Extracellulaire et Physiopathologie (MECuP), Institut des Materiaux, I-MAT (FD4122), CY Cergy Paris Université, France.
  • Carreiras F; Equipe de Recherche sur Les Relations Matrice Extracellulaire-Cellules, ERRMECe, (EA1391), Groupe Matrice Extracellulaire et Physiopathologie (MECuP), Institut des Materiaux, I-MAT (FD4122), CY Cergy Paris Université, France.
  • Kellouche S; Equipe de Recherche sur Les Relations Matrice Extracellulaire-Cellules, ERRMECe, (EA1391), Groupe Matrice Extracellulaire et Physiopathologie (MECuP), Institut des Materiaux, I-MAT (FD4122), CY Cergy Paris Université, France. Electronic address: sabrina.kellouche@cyu.fr.
Exp Cell Res ; 441(1): 114155, 2024 Aug 01.
Article em En | MEDLINE | ID: mdl-39002689
ABSTRACT
At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence especially because of the propensity of the OC cells to spread in the abdominal cavity leading to peritoneal metastasis. The influence of ascites on the development of pre-metastatic niches, and on the biological mechanisms leading to cancer cell colonization of the mesothelium, remains poorly understood. Here, we show that ascites weakens the mesothelium by affecting the morphology of mesothelial cells and by destabilizing their distribution in the cell cycle. Ascites also causes destabilization of the integrity of mesothelium by modifying the organization of cell junctions, but it does not affect the synthesis of N-cadherin and ZO-1 by mesothelial cells. Moreover, ascites induces disorganization of focal contacts and causes actin cytoskeletal reorganization potentially dependent on the activity of Rac1. Ascites allows the densification and reorganization of ECM proteins of the mesothelium, especially fibrinogen/fibrin, and indicates that it is a source of the fibrinogen and fibrin surrounding OC spheroids. The fibrin in ascites leads to the adhesion of OC spheroids to the mesothelium, and ascites promotes their disaggregation followed by the clearance of mesothelial cells. Both αV and α5ß1 integrins are involved. In conclusion ascites and its fibrinogen/fibrin composition affects the integrity of the mesothelium and promotes the integrin-dependent implantation of OC spheroids in the mesothelium.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Ascite / Fibrinogênio / Fibrina / Esferoides Celulares / Integrina alfa5beta1 / Microambiente Tumoral Limite: Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Ascite / Fibrinogênio / Fibrina / Esferoides Celulares / Integrina alfa5beta1 / Microambiente Tumoral Limite: Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article