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Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis
by
Visvader, Jane E.
, Murphy, Andrew J.
, Chen, Yunshun
, Yip, Raymond K. H.
, Hawkins, Edwin D.
, Capaldo, Bianca D.
, Pal, Bhupinder
, Lindeman, Geoffrey J.
, Smyth, Gordon K.
, Mouchemore, Kellie A.
, Anderson, Robin L.
, Rimes, Joel S.
, Surgenor, Elliot
, Vaillant, François
in
13/106
/ 13/31
/ 13/89
/ 14
/ 14/19
/ 59
/ 631/67/1347
/ 631/80/2373
/ 692/4028/67/1347
/ Animals
/ Blood vessels
/ Bone and Bones - diagnostic imaging
/ Bone and Bones - surgery
/ Bone imaging
/ Bone marrow
/ Bone Marrow - diagnostic imaging
/ Bone Marrow - surgery
/ Bone Neoplasms - diagnostic imaging
/ Bone Neoplasms - surgery
/ Bone remodeling
/ Breast cancer
/ Breast Neoplasms - surgery
/ Colonies
/ Colony-stimulating factor
/ Disease Progression
/ Endothelium
/ Granulocyte Colony-Stimulating Factor
/ Granulocytes
/ Humanities and Social Sciences
/ Humans
/ Imaging, Three-Dimensional
/ Leukocytes (granulocytic)
/ Mammary Neoplasms, Animal
/ Medical imaging
/ Metastases
/ Metastasis
/ Mice
/ Microenvironments
/ Microvasculature
/ Morbidity
/ multidisciplinary
/ Neoplasm Metastasis - diagnostic imaging
/ Neoplasm Metastasis - therapy
/ Neoplasms, Second Primary
/ Receptors, Colony-Stimulating Factor
/ Science
/ Science (multidisciplinary)
/ Solid tumors
/ Therapeutic targets
/ Tumor Microenvironment
/ Tumors
2021
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Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis
by
Visvader, Jane E.
, Murphy, Andrew J.
, Chen, Yunshun
, Yip, Raymond K. H.
, Hawkins, Edwin D.
, Capaldo, Bianca D.
, Pal, Bhupinder
, Lindeman, Geoffrey J.
, Smyth, Gordon K.
, Mouchemore, Kellie A.
, Anderson, Robin L.
, Rimes, Joel S.
, Surgenor, Elliot
, Vaillant, François
in
13/106
/ 13/31
/ 13/89
/ 14
/ 14/19
/ 59
/ 631/67/1347
/ 631/80/2373
/ 692/4028/67/1347
/ Animals
/ Blood vessels
/ Bone and Bones - diagnostic imaging
/ Bone and Bones - surgery
/ Bone imaging
/ Bone marrow
/ Bone Marrow - diagnostic imaging
/ Bone Marrow - surgery
/ Bone Neoplasms - diagnostic imaging
/ Bone Neoplasms - surgery
/ Bone remodeling
/ Breast cancer
/ Breast Neoplasms - surgery
/ Colonies
/ Colony-stimulating factor
/ Disease Progression
/ Endothelium
/ Granulocyte Colony-Stimulating Factor
/ Granulocytes
/ Humanities and Social Sciences
/ Humans
/ Imaging, Three-Dimensional
/ Leukocytes (granulocytic)
/ Mammary Neoplasms, Animal
/ Medical imaging
/ Metastases
/ Metastasis
/ Mice
/ Microenvironments
/ Microvasculature
/ Morbidity
/ multidisciplinary
/ Neoplasm Metastasis - diagnostic imaging
/ Neoplasm Metastasis - therapy
/ Neoplasms, Second Primary
/ Receptors, Colony-Stimulating Factor
/ Science
/ Science (multidisciplinary)
/ Solid tumors
/ Therapeutic targets
/ Tumor Microenvironment
/ Tumors
2021
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Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis
by
Visvader, Jane E.
, Murphy, Andrew J.
, Chen, Yunshun
, Yip, Raymond K. H.
, Hawkins, Edwin D.
, Capaldo, Bianca D.
, Pal, Bhupinder
, Lindeman, Geoffrey J.
, Smyth, Gordon K.
, Mouchemore, Kellie A.
, Anderson, Robin L.
, Rimes, Joel S.
, Surgenor, Elliot
, Vaillant, François
in
13/106
/ 13/31
/ 13/89
/ 14
/ 14/19
/ 59
/ 631/67/1347
/ 631/80/2373
/ 692/4028/67/1347
/ Animals
/ Blood vessels
/ Bone and Bones - diagnostic imaging
/ Bone and Bones - surgery
/ Bone imaging
/ Bone marrow
/ Bone Marrow - diagnostic imaging
/ Bone Marrow - surgery
/ Bone Neoplasms - diagnostic imaging
/ Bone Neoplasms - surgery
/ Bone remodeling
/ Breast cancer
/ Breast Neoplasms - surgery
/ Colonies
/ Colony-stimulating factor
/ Disease Progression
/ Endothelium
/ Granulocyte Colony-Stimulating Factor
/ Granulocytes
/ Humanities and Social Sciences
/ Humans
/ Imaging, Three-Dimensional
/ Leukocytes (granulocytic)
/ Mammary Neoplasms, Animal
/ Medical imaging
/ Metastases
/ Metastasis
/ Mice
/ Microenvironments
/ Microvasculature
/ Morbidity
/ multidisciplinary
/ Neoplasm Metastasis - diagnostic imaging
/ Neoplasm Metastasis - therapy
/ Neoplasms, Second Primary
/ Receptors, Colony-Stimulating Factor
/ Science
/ Science (multidisciplinary)
/ Solid tumors
/ Therapeutic targets
/ Tumor Microenvironment
/ Tumors
2021
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Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis
Journal Article
Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis
2021
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Overview
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.
The visualisation of the bone metastasis process in a spatial temporal manner is lacking. Here, the authors use three-dimensional quantitative imaging and show that mouse mammary tumour cells preferentially home to endothelial subtype type H vessels within the bone marrow and remodel this vasculature by producing granulocyte-colony stimulating factor.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 13/89
/ 14
/ 14/19
/ 59
/ Animals
/ Bone and Bones - diagnostic imaging
/ Bone Marrow - diagnostic imaging
/ Bone Neoplasms - diagnostic imaging
/ Colonies
/ Granulocyte Colony-Stimulating Factor
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Neoplasm Metastasis - diagnostic imaging
/ Neoplasm Metastasis - therapy
/ Receptors, Colony-Stimulating Factor
/ Science
/ Tumors
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