Tumor-associated Macrophages Promote the Metastatic Potential of Thyroid Papillary Cancer by Releasing CXCL8
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, via les récepteurs CXCL8, les macrophages associés aux tumeurs favorisent le processus métastatique d'un carcinome papillaire de la thyroïde
Tumor-associated macrophages (TAMs) can promote cancer initiation and progression by releasing cytokines. Previously, we have found the density of TAMs correlated with lymph node metastasis in papillary thyroid carcinoma (PTC). However the mechanisms of how TAMs promote PTC progression remain unclear.In this study, we first showed that the TAMs density in the tumor core was associated with progressive PTC features and TAMs conditioned medium enhanced PTC cells invasion. Cytokine profiling identified a mixed M1/M2 phenotype and CXCL8 was the most consistently abundant cytokine in PTC-derived TAMs. CXCL8 receptors, CXCR1 and CXCR2, were positively stained in PTC cell lines and tissues, though no association with lymph node metastasis or extrathyroid extension. PTC cell invasion was abrogated by anti-CXCL8 neutralizing antibody, while addition of exogenous recombinant human CXCL8 enhanced the invasiveness. More importantly, CXCL8 promoted PTC metastasis in vivo. No difference was found for TAMs derived CXCL8 expression in patients with and without lymph node metastasis or extrathyroid extension. These findings indicated that TAMs may facilitate PTC cell metastasis through CXCL8 and its paracrine interaction with CXCR1/2.
http://carcin.oxfordjournals.org/content/early/2014/03/06/carcin.bgu060.abstract