The perivascular niche regulates breast tumour dormancy Academic Article uri icon

Overview

MeSH Major

  • Bone Marrow Neoplasms
  • Brain Neoplasms
  • Breast Neoplasms
  • Endothelium, Vascular
  • Lung Neoplasms
  • Neoplasm, Residual
  • Neovascularization, Pathologic
  • Pericytes

abstract

  • In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumour cells (DTCs) are kept dormant, and what wakes them up, are fundamental problems in tumour biology. To address these questions, we used metastasis assays in mice and showed that dormant DTCs reside on microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumour-promoting factors derived from endothelial tip cells. Our work reveals that stable microvasculature constitutes a dormant niche, whereas sprouting neovasculature sparks micrometastatic outgrowth.

publication date

  • July 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3826912

Digital Object Identifier (DOI)

  • 10.1038/ncb2767

PubMed ID

  • 23728425

Additional Document Info

start page

  • 807

end page

  • 17

volume

  • 15

number

  • 7