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Aggressive prostate cancer is associated with pericyte dysfunction.

Anabel Martinez-Romero1,2, Ane Martinez-Larrinaga1,2,3,4, Joaquim Grego-Bessa1,5

  • 1Endothelial Pathobiology and Microenvironment Group, Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Catalonia, Spain.

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Summary

Prostate pericytes, crucial for blood vessel stability, become dysfunctional in cancer, not lost. Transforming growth factor-beta (TGF-β) drives this dysfunction, impacting tumor vascularization and permeability.

Keywords:
TGFβ signalingpericytesprostate cancervessels

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Area of Science:

  • Vascular Biology
  • Cancer Pathogenesis
  • Cellular Reprogramming

Background:

  • Pericytes are vital mural cells regulating blood vessel stability and permeability.
  • Aberrant tumor vascularization is a hallmark of cancer, but pericyte roles are unclear.
  • Prostate cancer progression involves complex changes in tumor microenvironment.

Purpose of the Study:

  • To investigate the molecular reprogramming of prostate pericytes during cancer.
  • To determine the contribution of pericytes to prostate cancer pathogenesis and progression.
  • To identify molecular signatures distinguishing pericyte abundance from function.

Main Methods:

  • Combined computational and experimental approaches.
  • Analysis of human prostate cancer and murine models.
  • Single-cell RNA sequencing.

Main Results:

  • Prostate tumors show prognostic potential linked to endothelial-pericyte imbalance.
  • Pericyte dysfunction, not loss, characterizes prostate tumors, with altered marker expression.
  • Transforming growth factor-beta (TGF-β) drives pericyte dysfunction via molecular changes.
  • Dysfunctional pericytes correlate with reduced contractility markers, enlarged vascular lumens, and increased permeability.

Conclusions:

  • Pericyte dysfunction, rather than reduced numbers, is key in tumor progression.
  • TGF-β signaling is a critical regulator of pericyte dysfunction in prostate cancer.
  • Understanding pericyte function is crucial for targeting tumor vascularization.