ANAPLASTIC THYROID CANCER-DERIVED CONDITIONED MEDIUM INDUCES POLARIZATION OF THP-1 CELLS THROUGH UPREGULATION OF STAT3

FOZZATTI, L; PARK, S; STEMPIN, C; CHENG, SY; PELLIZAS, CG

Buenos Aires

Congreso; XVII Latin American Thyroid Congress; 2019

Latin American Thyroid Society

Introduction: Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors. Characterized by its undifferentiated cells, itspreads quickly to distant organs and does not respond well to standardized therapy. Tumor-associated macrophages (TAMs) are themost evident cells in all ATC representing more than 50% of the nucleated cells and there is a correlation between the number ofTAMs and poor prognosis. Macrophage (Mφ) phenotype has been classified in pro-inflammatory (M1) and anti-inflammatory (M2).TAMs mostly have a tumor-promoting M2 phenotype. How tumor cytokines reprogram Mφ phenotype during the developing ofATC is poorly understood. Objectives: To investigate the effect of soluble factors secreted by ATC cells on the modulation of Mφphenotype. Methods: THP-1 cells (human monocytes) were exposed to conditioned media produced by human ATC cells (ATCCM).Mφ proliferation and polarization were assessed by flow cytometry, RT-qPCR and Western blot analysis. Results: ATC-CMstrongly influenced the phenotype of THP-1 cells. The changes involved increased expression of CCL13, CLEC7A and CD206, widelyconsidered as M2 markers of TAMs. However, the levels of classical M1 markers were not modified. The ATC-CM decreased theproliferation of THP-1 cells delaying their cell cycle progression from the G0/G1 phase to the S phase. The ATC-CM also increasedthe mRNA expression of the pro-inflammatory cytokine IL-6 and the phosphorylation of STAT3 in THP-1 cells. Conclusion: Thesestudies suggest that ATC cells produce soluble factors that can reprogram Mφ phenotype, most probably into M2 TAMs. A betterunderstanding of these events may represent a promising basis for the development of new therapies for ATC. Conflict of interest:None declared.