Survivin drives tumor-associated macrophage reprogramming: a novel mechanism with potential impact for obesity

• DOI: 10.1007/s13402-021-00597-x
• Publication Date: 2021-03-12T11:09:03Z
• Authors: E. Benaiges; V. Ceperuelo-Mall...; A. Madeira; R. Bosch; C. Núñez-Roa; M. Ejarque; E. Maymó-Masip; I. Huber-Ruano; M. Lejeune; J. Vendrell; S. Fernández-Veledo
• Keywords: Survivin; Adipose tissue macrophages

Abstract Purpose Recent studies point to adipose-derived stem cells (ASCs) as a link between obesity and cancer. We aimed determine whether survivin, which is highly secreted by ASCs from subjects with obesity, might drive pro-tumoral phenotype in macrophages. Methods The effect of ASC conditioned medium on the macrophage was assessed expression studies. Survivin intracellular localization internalization were examined subcellular fractionation immunofluorescence, respectively. Loss- gain-of-function performed using adenoviral vectors, gene patterns, migration invasion capacities cancer examined. Heterotypic cultures ASCs, macrophages established mimic tumor microenvironment. Survivin-blocking experiments used impact survivin both cells. Immunohistochemical analysis ascitic fluids patients healthy controls. Results found that obese-derived induced phenotypic switch characterized pro- anti-inflammatory markers. Macrophages internalize extracellular generating hybrid tumor-associated included secretion survivin. Exogenous generated similar enhanced malignant characteristics mechanism dependent phosphorylation at threonine 34. synergistically boosted malignancy Importantly, mainly detected ascites-associated diagnosis. Conclusion Our data indicate may serve molecular novel marker for