The stimulation of A3 adenosine receptors reduces bone-residing breast cancer in a rat preclinical model

Amongst cancers with poor prognosis those originating from breast commonly metastasise to the skeleton for the high affinity of breast cancer cells to bone. A3 adenosine receptor (A3AR) agonists were found to be potent anti-tumour agents even if their effect on bone-residing breast cancer has not yet been investigated. An animal model of surgery-induced metastasis was used to mimic the human condition in an attempt to develop a novel effective treatment strategy. Sprague-Dawley rats receiving intra-tibial injections of syngeneic MRMT-1 rat mammary gland carcinoma cells developed cancer-associated osteolytic lesions and structural damage that were monitored by microcomputed tomography imaging and histological analysis. To address the involvement of A3ARs in tumour-related signalling pathway, A3AR expression and functional role were analysed in MRMT-1 cells. The effect of chronic treatment with an A3AR agonist, 2-chloro-N 6-(3-iodobenzyl)-adenosine-5′-N-methyl-uronamide (Cl-IB-MECA) in c...