β3-Adrenoreceptor Blockade Induces Stem Cells Differentiation in Melanoma Microenvironment

摘要: Although there is an increasing evidence that cancer stem cell (CSC) niches in the tumor microenvironment (TME) plays a crucial role sustaining solid tumors progression, several molecular players involved this regulation still remain unknown. The of β-adrenergic signaling enhancing growth through β2-adrenoreceptors (β2-ARs) has been confirmed different models, but played by β3-adrenergic receptor (β3-AR) recently emerged. Previous studies showed β3-AR promotes activation stromal cells TME, and leads to melanoma malignancy progression inflammation, angiogenesis, immunotolerance. Here we show B16 melanoma-bearing mice, pharmacological blockade able reduce expression CSC markers, induce differentiated phenotype hematopoietic subpopulations TME. In particular, cytofluorimetric analysis (FACS) mass shows antagonist SR59230A differentiation as indicated increased ratios lymphoid/hematopoietic (HSCs) myeloid progenitor cells/HSCs, increases number Ter119 natural killer (NK) precursor cells, granulocyte precursors, indicating active hematopoiesis within tissue. Moreover, antagonism induces mesenchymal (MSC) into adipocytes subtracting potential renewal compartment these cells. demonstrate TME inducing at expense stemness traits could possibly have favorable effect on control progression.