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A new study from the Kennedy Institute of Rheumatology reveals a role for blood vessels in promoting therapy resistance of cancer metastasis in bone.

Confocal image showing subtypes of blood vessels (red, green and white) in bone. The new research links certain types of blood vessel cells to therapy resistance in tumour metastasis.

The research led by Dr Anjali Kusumbe’s team at the Kennedy Institute and published in JCI Insight shows that cells called pericytes that attach to blood vessels can halt the growth of cancer cells that have travelled from the primary tumour to bones. 

The researchers found increased numbers of pericytes in bones following chemotherapy or radiation, together with more of the proteins they secrete that keep cancer cells in check. As chemotherapy targets actively diving cells, these findings suggest pericytes might promote resistance to therapy.

Speaking of the research, Anjali said, “This is an offshoot of our research programme on understanding the vascular maladaptation during ageing, bone diseases and cancer. Blood vessels provide inductive signals during organ growth and form nurturing niches for multiple adult stem cells in the body. Our study shows that the vascular niches in bone respond differentially to cancer therapies and secrete factors to protect cancer cells during treatments”.        

Treatment with cancer therapies caused blood vessels in bone to secrete more of a molecule called PDGF2, which activates pericytes. Anjali explains “We identified blood flow and PDGF as a regulator of pericyte expansion in bone during treatment with cancer therapies. Use of blood flow modulators in combination with conventional cancer therapies render disseminated tumour cells in bones susceptible to these therapies, providing a possible strategy to target these cells to prevent bone metastasis”.     

Pericytes became less effective at subduing cancer cells with age, which may explain why cancer returns in the bones of some patients many years after treatment. 

The researchers are now focusing their attention on identifying therapeutic targets in the bone marrow microenvironment for managing age-related metastatic relapse. 

The work was supported by the European Research Council, Leuka, Medical Research Council, Royal Society, CRUK Development Fund and the Kennedy Trust for Rheumatology Research.

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