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

PARK, SUNMI; PELLIZAS, CLAUDIA GABRIELA; STEMPIN, CINTHIA; FOZZATTI LAURA; CHENG SHEUE-YANN

Buenos Aires

Congreso; XVII Congreso de la Sociedad Latinoamericana de Tiroides (SLAT).; 2019

Sociedad Latinoamericana de Tiroides

Introduction: Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors. Characterized by its undifferentiated cells, it spreads quickly to distant organs and does not respond well to standardized therapy. Tumor-associated macrophages (TAMs) are the most evident cells in all ATC representing more than 50% of the nucleated cells and there is a correlation between the number of TAMs 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 of ATC is poorly understood.Aim: To investigate the effect of soluble factors secreted by ATC cells on the modulation of Mφ phenotype.Methods: THP-1 cells (human monocytes) were exposed to conditioned media produced by human ATC cells (ATC-CM). Mφ proliferation and polarization were assessed by flow cytometry, RT-qPCR and Western blot analysis.Results: ATC-CM strongly influenced the phenotype of THP-1 cells. The changes involved increased expression of CCL13, CLEC7A and CD206, widely considered as M2 markers of TAMs. However, the levels of classical M1 markers were not modified. The ATC-CM decreased the proliferation of THP-1 cells delaying their cell cycle progression from the G0/G1 phase to the S phase. The ATC-CM also increased the mRNA expression of the pro-inflammatory cytokine IL-6 and the phosphorylation of STAT3 in THP-1 cells.Conclusions and Discussion: These studies suggest that ATC cells produce soluble factors that can reprogram Mφ phenotype, most probably into M2 TAMs. A better understanding of these events may represent a promising basis for the development of new therapies for ATC.