CONICET | Buscador de Institutos y Recursos Humanos

Wnt/β-catenin pathway is intricately involved in pathogenesis of several cancers and many therapeutic strategies have been developed with the aim to inhibit Wnt-pathway. During tumor progression, circulating monocytes and macrophages are actively recruited into tumor microenvironment (TME) where they can promote tumor initiation, angiogenesis, metastasis and suppression of adaptive immunity. Tumor associated macrophages (TAM) closely resemble the M2-polarized macrophages and its accumulation in tumors correlates with a poor clinical outcome. We have recently reported that pharmacological inhibition of Wnt signaling, inhibits arginase-1 activity and induces an M1-like phenotype in T. cruzi infected macrophages. Because evidences show that TAM shift their functional phenotypes in response to various microenvironmental signals generated from TME, Wnt proteins secreted by tumor and TME cells could be important for regulate the activation state of TAM and consequently their role in tumor progression. While the role of β-catenin activation pathway is controversial in the metastasic spread of melanoma, nuclear β-catenin correlates with a higher proliferation and a loss of differentiation in anaplastic thyroid carcinoma (ATC). Here, we evaluated the ability of conditioned media from melanoma (B16F10-OVA) and ATC cells (8505C) to up-regulate β-catenin expression and activation in bone marrow derived macrophages (BMM) from B6 mice and THP-1 human monocytes/macrophages, respectively. Conditioned medium obtained from B16F10-OVA cells as well as from ATC cells induced significant accumulation of β-catenin in BMM (p=0.009) and THP-1 monocytes (p=0.05) and macrophages (p=0.02) after 24 h of culture. In addition, conditioned medium from B6 mice derived-tumors alone or in the presence of LPS induced significant secretion of IL-10 (p