Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway.
Bottom Line: A marked reduction in the number of tumour-associated macrophages was paralleled by a significant decrease in tumour vascularization.The local production of vascular endothelial growth factor and interleukin-10 was drastically down-regulated in favour of interferon-γ production.These data indicate that clinically achievable doses of ZA inhibit spontaneous mammary cancerogenesis by targeting the local microenvironment, as shown by a decreased tumour vascularization, a reduced number of tumour-associated macrophages and their reverted polarization from M2 to M1 phenotype.
Affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero Universitaria S. Giovanni Battista di Torino, Torino, Italy. email@example.comShow MeSH
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Mentions: As VEGF plays a key role in inducing a M2 polarization of TAMs [31, 32], we evaluated whether the decrease of VEGF observed in the tumour microenvironment of ZA-treated mice was associated with a recovered M1 functional program. Indeed, TAMs of 18-week-old control mice expressed IL-10 (Fig. 4A) but not IFN-γ (Fig. 4C), whereas TAMs of ZA-treated mice stained negative for IL-10 (Fig. 4B), and became strongly positive for IFN- g (Fig. 4D).
Affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero Universitaria S. Giovanni Battista di Torino, Torino, Italy. firstname.lastname@example.org