Evidence map›Paper›PMID 34209088›Full record

ArticleInternational journal of molecular sciences2021

Behind Brain Metastases Formation: Cellular and Molecular Alterations and Blood-Brain Barrier Disruption.

Joana Godinho-Pereira, Ana Rita Garcia, Inês Figueira, Rui Malhó, Maria Alexandra Brito

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Cell-cell communication characteristics in breast cancer metastasis.Cell communication and signaling : CCS · 2024
    Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Brain metastasis in breast cancer: focus on genes and signaling pathways involved, blood-brain barrier and treatment strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Review
  15. Article
  16. The Journey of Cancer Cells to the Brain: Challenges and Opportunities.International journal of molecular sciences · 2023
    Review
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Joana Godinho-PereiraiMed.ULisboa-Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.ORCID 0000-0002-8219-6240
Ana Rita GarciaiMed.ULisboa-Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
Inês FigueiraiMed.ULisboa-Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.ORCID 0000-0003-4639-6883
Rui MalhóBioISI-Biosystems and Integrative Sciences Institute, Faculty of Sciences, Universidade de Lisboa, Campo Grande 016, 1749-016 Lisbon, Portugal.
Maria Alexandra BritoiMed.ULisboa-Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.ORCID 0000-0002-8493-4649
University of Lisbon · PT

Funding

Fundação para a Ciência e a Tecnologia PTDC/MED-ONC/29402/2017, UIDP/04138/2020, UIDB/04138/2020, SFRH/BD/145522/2019, and 2020.07115.BD.
6 · The paper itself

Abstract

Breast cancer (BC) brain metastases is a life-threatening condition to which accounts the poor understanding of BC cells' (BCCs) extravasation into the brain, precluding the development of preventive strategies. Thus, we aimed to unravel the players involved in the interaction between BCCs and blood-brain barrier (BBB) endothelial cells underlying BBB alterations and the transendothelial migration of malignant cells. We used brain microvascular endothelial cells (BMECs) as a BBB in vitro model, under conditions mimicking shear stress to improve in vivo-like BBB features. Mixed cultures were performed by the addition of fluorescently labelled BCCs to distinguish individual cell populations. BCC-BMEC interaction compromised BBB integrity, as revealed by junctional proteins (β-catenin and zonula occludens-1) disruption and caveolae (caveolin-1) increase, reflecting paracellular and transcellular hyperpermeability, respectively. Both BMECs and BCCs presented alterations in the expression pattern of connexin 43, suggesting the involvement of the gap junction protein. Myosin light chain kinase and phosphorylated myosin light chain were upregulated, revealing the involvement of the endothelial cytoskeleton in the extravasation process. β4-Integrin and focal adhesion kinase were colocalised in malignant cells, reflecting molecular interaction. Moreover, BCCs exhibited invadopodia, attesting migratory properties. Collectively, hub players involved in BC brain metastases formation were unveiled, disclosing possible therapeutic targets for metastases prevention.

Indexed as

Gene Regulatory NetworksAnimalsbeta CateninBlood-Brain BarrierBrain NeoplasmsBreast NeoplasmsCaveolin 1Cell Culture TechniquesCell Line, TumorConnexin 43FemaleGene Expression Regulation, NeoplasticHumansMicePhosphorylationShear Strengthbeta CateninCAV1 protein, humanCaveolin 1Connexin 43CTNNB1 protein, humanGJA1 protein, humanTJP1 protein, humanZonula Occludens-1 Proteinadhesionblood–brain barrierbreast cancer brain metastasescellular communicationextravasationparacellular and transcellular migration

Identifiers

PMID34209088
PMCPMC8268492
OpenAlexW3175472314

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.