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Picturing Breast Cancer Brain Metastasis Development to Unravel Molecular Players and Cellular Crosstalk.
Figueira, Inês; Galego, Sofia; Custódio-Santos, Tânia; Vicente, Raquel; Molnár, Kinga; Haskó, Janos; Malhó, Rui; Videira, Mafalda; Wilhelm, Imola; Krizbai, István; Brito, Maria Alexandra.
Afiliação
  • Figueira I; Farm-ID-Associação da Faculdade de Farmácia para a Investigação e Desenvolvimento, 1649-003 Lisbon, Portugal.
  • Galego S; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
  • Custódio-Santos T; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
  • Vicente R; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
  • Molnár K; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
  • Haskó J; Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network (ELKH), 6726 Szeged, Hungary.
  • Malhó R; Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network (ELKH), 6726 Szeged, Hungary.
  • Videira M; BioISI, BioSystems and Integrative Sciences Institute, Faculty of Sciences, Universidade de Lisboa, 1749-016 Lisbon, Portugal.
  • Wilhelm I; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
  • Krizbai I; Department of Pharmacy, Pharmacology and Health Technologies, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
  • Brito MA; Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network (ELKH), 6726 Szeged, Hungary.
Cancers (Basel) ; 13(4)2021 Feb 22.
Article em En | MEDLINE | ID: mdl-33671551
With breast cancer (BC) therapy improvements, the appearance of brain metastases has been increasing, representing a life-threatening condition. Brain metastasis formation involves BC cell (BCC) extravasation across the blood-brain barrier (BBB) and brain colonization by unclear mechanisms. We aimed to disclose the actors involved in BC brain metastasis formation, focusing on BCCs' phenotype, growth factor expression, and signaling pathway activation, correlating with BBB alterations and intercellular communication. Hippocampi of female mice inoculated with 4T1 BCCs were examined over time by hematoxylin-eosin, immunohistochemistry and immunofluorescence. Well-established metastases were observed at seven days, increasing thereafter. BCCs entering brain parenchyma presented mesenchymal, migratory, and proliferative features; however, with time, they increasingly expressed epithelial markers, reflecting a mesenchymal-epithelial transition. BCCs also expressed platelet-derived growth factor-B, ß4 integrin, and focal adhesion kinase, suggesting autocrine and/or paracrine regulation with adhesion signaling activation, while balance between Rac1 and RhoA was associated with the motility status. Intercellular communication via gap junctions was clear among BCCs, and between BCCs and endothelial cells. Thrombin accumulation, junctional protein impairment, and vesicular proteins increase reflect BBB alterations related with extravasation. Expression of plasmalemma vesicle-associated protein was increased in BCCs, along with augmented vascularization, whereas pericyte contraction indicated mural cells' activation. Our results provide further understanding of BC brain metastasis formation, disclosing potential therapeutic targets.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Portugal

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Portugal