Physical Poster + E-Poster Presentation 34th Lorne Cancer Conference 2022

Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis (#255)

Raymond Yip 1 , Joel Rimes 1 , Bianca Capaldo 1 , Francois Vaillant 1 , Kellie Mouchemore 2 , Bhupinder Pal 1 3 , Yunshun Chen 1 , Elliot Surgenor 1 , Andrew Murphy 4 , Robin Anderson 2 , Gordon Smyth 1 , Geoffrey Lindeman 1 5 , Edwin Hawkins 1 , Jane Visvader 1
  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Translational Breast Cancer Program, Olivia Newton-John Cancer Research Institute, Heidelberg , VIC, Australia
  3. Single Cell Cancer Genomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia
  4. Division of Immunometabolism, Baker Heart & Diabetes Institute, Melbourne
  5. Parkville Familial Cancer Centre and Department of Medical Oncology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, VIC, Australia

Bone marrow is a preferred metastatic site for multiple solid tumours. 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.