Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis

Nat Commun. 2021 Nov 26;12(1):6920. doi: 10.1038/s41467-021-26556-6.


Bone marrow is a preferred metastatic site for multiple solid tumours and is associated with poor prognosis and significant morbidity. Accumulating evidence indicates that cancer cells colonise specialised niches within the bone marrow to support their long-term propagation, but the precise location and mechanisms that mediate niche interactions are unknown. Using breast cancer as a model of solid tumour metastasis to the bone marrow, we applied large-scale quantitative three-dimensional imaging to characterise temporal changes in the bone marrow microenvironment during disease progression. We show that mouse mammary tumour cells preferentially home to a pre-existing metaphyseal domain enriched for type H vessels. Metastatic lesion outgrowth rapidly remodelled the local vasculature through extensive sprouting to establish a tumour-supportive microenvironment. The evolution of this tumour microenvironment reflects direct remodelling of the vascular endothelium through tumour-derived granulocyte-colony stimulating factor (G-CSF) in a hematopoietic cell-independent manner. Therapeutic targeting of the metastatic niche by blocking G-CSF receptor inhibited pathological blood vessel remodelling and reduced bone metastasis burden. These findings elucidate a mechanism of 'host' microenvironment hijacking by mammary tumour cells to subvert the local microvasculature to form a specialised, pro-tumorigenic niche.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow* / diagnostic imaging
  • Bone Marrow* / surgery
  • Bone Neoplasms* / diagnostic imaging
  • Bone Neoplasms* / surgery
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / surgery
  • Breast Neoplasms* / surgery
  • Disease Progression
  • Granulocyte Colony-Stimulating Factor
  • Humans
  • Imaging, Three-Dimensional
  • Mammary Neoplasms, Animal*
  • Mice
  • Neoplasm Metastasis* / diagnostic imaging
  • Neoplasm Metastasis* / therapy
  • Neoplasms, Second Primary
  • Receptors, Colony-Stimulating Factor
  • Tumor Microenvironment*


  • CSF3R protein, human
  • Receptors, Colony-Stimulating Factor
  • Granulocyte Colony-Stimulating Factor