The Role of Sinusoidal Endothelial Cells in the Axis of Inflammation and Cancer Within the Liver

Alex L Wilkinson, Maria Qurashi, Shishir Shetty

Research output: Contribution to journalReview articlepeer-review

5 Citations (Scopus)
227 Downloads (Pure)

Abstract

Liver sinusoidal endothelial cells (LSEC) form a unique barrier between the liver sinusoids and the underlying parenchyma, and thus play a crucial role in maintaining metabolic and immune homeostasis, as well as actively contributing to disease pathophysiology. Whilst their endocytic and scavenging function is integral for nutrient exchange and clearance of waste products, their capillarisation and dysfunction precedes fibrogenesis. Furthermore, their ability to promote immune tolerance and recruit distinct immunosuppressive leukocyte subsets can allow persistence of chronic viral infections and facilitate tumour development. In this review, we present the immunological and barrier functions of LSEC, along with their role in orchestrating fibrotic processes which precede tumourigenesis. We also summarise the role of LSEC in modulating the tumour microenvironment, and promoting development of a pre-metastatic niche, which can drive formation of secondary liver tumours. Finally, we summarise closely inter-linked disease pathways which collectively perpetuate pathogenesis, highlighting LSEC as novel targets for therapeutic intervention.

Original languageEnglish
Article number990
JournalFrontiers in Physiology
Volume11
DOIs
Publication statusPublished - 28 Aug 2020

Bibliographical note

Copyright © 2020 Wilkinson, Qurashi and Shetty.

Keywords

  • capillarisation
  • endothelial dysfunction
  • fibrosis
  • hepatocellular carcinoma
  • inflammation
  • leukocyte recruitment
  • liver sinusoidal endothelial cell
  • metastasis

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