Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/28222
Title: Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis.
Austin Authors: Yip, Raymond K H;Rimes, Joel S;Capaldo, Bianca D;Vaillant, François;Mouchemore, Kellie A;Pal, Bhupinder;Chen, Yunshun;Surgenor, Elliot;Murphy, Andrew J;Anderson, Robin L ;Smyth, Gordon K;Lindeman, Geoffrey J;Hawkins, Edwin D;Visvader, Jane E
Affiliation: Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
Department of Immunology, Monash University, Melbourne, VIC, Australia
Division of Immunometabolism, Baker Heart & Diabetes Institute, Melbourne, VIC, Australia
School of Cancer Medicine, La Trobe University, Bundoora, VIC, 3086, Australia
Olivia Newton-John Cancer Research Institute
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, 3010, Australia
ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
Department of Medicine, The University of Melbourne, Parkville, VIC, 3010, Australia
Department of Medical Oncology and Parkville Familial Cancer Centre, The Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Parkville, VIC, 3050, Australia
Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3010, Australia
Issue Date: 26-Nov-2021
Date: 2021-11-26
Publication information: Nature Communications 2021; 12(1): 6920
Abstract: 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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/28222
DOI: 10.1038/s41467-021-26556-6
ORCID: 0000-0003-2698-7686
0000-0001-6488-2784
0000-0003-3229-3760
0000-0002-3684-4331
0000-0003-4911-5653
0000-0001-7039-7777
0000-0001-9221-2892
0000-0001-9386-2416
0000-0002-3686-8261
0000-0001-9173-6977
Journal: Nature Communications
PubMed URL: 34836954
Type: Journal Article
Appears in Collections:Journal articles

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