Imperial College London
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DrSaravanaRamasamy

Faculty of Medicine, National Heart & Lung Institute

Advanced Research Fellow
 
 
 
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Contact

 

+44 (0)20 3313 1182s.ramasamy Website

 
 
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Location

 

CRB 2003Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Singh:2019:10.1172/jci.insight.125679,
author = {Singh, A and Veeriah, V and Xi, P and Labella, R and Chen, J and Romeo, SG and Ramasamy, SK and Kusumbe, AP},
doi = {10.1172/jci.insight.125679},
journal = {JCI Insight},
title = {Angiocrine signals regulate quiescence and therapy resistance in bone metastasis.},
url = {http://dx.doi.org/10.1172/jci.insight.125679},
volume = {4},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Bone provides supportive microenvironments for hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) and is a frequent site of metastasis. While incidences of bone metastases increase with age, the properties of the bone marrow microenvironment that regulate dormancy and reactivation of disseminated tumor cells (DTCs) remain poorly understood. Here, we elucidate the age-associated changes in the bone secretome that trigger proliferation of HSCs, MSCs, and DTCs in the aging bone marrow microenvironment. Remarkably, a bone-specific mechanism involving expansion of pericytes and induction of quiescence-promoting secretome rendered this proliferative microenvironment resistant to radiation and chemotherapy. This bone-specific expansion of pericytes was triggered by an increase in PDGF signaling via remodeling of specialized type H blood vessels in response to therapy. The decline in bone marrow pericytes upon aging provides an explanation for loss of quiescence and expansion of cancer cells in the aged bone marrow microenvironment. Manipulation of blood flow - specifically, reduced blood flow - inhibited pericyte expansion, regulated endothelial PDGF-B expression, and rendered bone metastatic cancer cells susceptible to radiation and chemotherapy. Thus, our study provides a framework to recognize bone marrow vascular niches in age-associated increases in metastasis and to target angiocrine signals in therapeutic strategies to manage bone metastasis.
AU  - Singh,A
AU  - Veeriah,V
AU  - Xi,P
AU  - Labella,R
AU  - Chen,J
AU  - Romeo,SG
AU  - Ramasamy,SK
AU  - Kusumbe,AP
DO  - 10.1172/jci.insight.125679
PY  - 2019///
SN  - 2379-3708
TI  - Angiocrine signals regulate quiescence and therapy resistance in bone metastasis.
T2  - JCI Insight
UR  - http://dx.doi.org/10.1172/jci.insight.125679
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31292293
UR  - https://insight.jci.org/articles/view/125679
UR  - http://hdl.handle.net/10044/1/71498
VL  - 4
ER  -
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