Author, as appears in the article.: Benaiges E; Ceperuelo-Mallafré V; Madeira A; Bosch R; Núñez-Roa C; Ejarque M; Maymó-Masip E; Huber-Ruano I; Lejeune M; Vendrell J; Fernández-Veledo S

Department: Bioquímica i Biotecnologia Ciències Mèdiques Bàsiques Medicina i Cirurgia

URV's Author/s: Benaiges Moragrega, Ester / Bosch Príncep, Ramon / Ceperuelo Mallafré, Maria Victoria / Fernandez Veledo, Sonia / Lejeune, Marylène Marie / Maymo Masip, Elsa / Vendrell Ortega, Juan José

Keywords: Tumor-associated macrophages Survivin Obesity Cancer Adipose-derived stem cells

Abstract: © 2021, The Author(s). Purpose: Recent studies point to adipose-derived stem cells (ASCs) as a link between obesity and cancer. We aimed to determine whether survivin, which is highly secreted by ASCs from subjects with obesity, might drive a pro-tumoral phenotype in macrophages. Methods: The effect of ASC conditioned medium on the macrophage phenotype was assessed by expression studies. Survivin intracellular localization and internalization were examined by subcellular fractionation and immunofluorescence, respectively. Loss- and gain-of-function studies were performed using adenoviral vectors, and gene expression patterns, migration and invasion capacities of cancer cells were examined. Heterotypic cultures of ASCs, macrophages and cancer cells were established to mimic the tumor microenvironment. Survivin-blocking experiments were used to determine the impact of survivin on both macrophages and cancer cells. Immunohistochemical analysis of survivin was performed in macrophages from ascitic fluids of cancer patients and healthy controls. Results: We found that obese-derived ASCs induced a phenotypic switch in macrophages characterized by the expression of both pro- and anti-inflammatory markers. Macrophages were found to internalize extracellular survivin, generating hybrid macrophages with a tumor-associated phenotype that included secretion of survivin. Exogenous expression of survivin in macrophages generated a similar phenotype and enhanced the malignant characteristics of cancer cells by a mechanism dependent on survivin phosphorylation at threonine 34. Survivin secreted by both ASCs from subjects with obesity and tumor-associated macrophages synergistically boosted the malignancy of cancer cells. Importantly, survivin was mainly detected in ascites-associated macrophages from patients with a malignant diagnosis. Conclusion: Our data indicate that survivin may serve as a molecular link between obesity and cancer and as a novel marker for tumor-associated macrophages.

Thematic Areas: Pathology Oncology Odontología Molecular medicine Medicine (miscellaneous) Medicina iii Medicina ii Medicina i Interdisciplinar Farmacia Ciências biológicas iii Ciências biológicas i Ciência da computação Cell biology Cancer research Biotecnología

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: ramon.bosch@urv.cat sonia.fernandez@urv.cat elsa.maymo@urv.cat victoria.ceperuelo@urv.cat marylenemarie.lejeune@urv.cat juanjose.vendrell@urv.cat ester.benaiges@urv.cat ramon.bosch@urv.cat

Author identifier: 0000-0003-2906-3788 0000-0002-9133-3120 0000-0002-4460-9761 0000-0001-8441-9404 0000-0002-6994-6115

Record's date: 2023-10-07

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://link.springer.com/article/10.1007%2Fs13402-021-00597-x

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Cellular Oncology. 44 (4): 777-792

APA: Benaiges E; Ceperuelo-Mallafré V; Madeira A; Bosch R; Núñez-Roa C; Ejarque M; Maymó-Masip E; Huber-Ruano I; Lejeune M; Vendrell J; Fernández-Veledo S (2021). Survivin drives tumor-associated macrophage reprogramming: a novel mechanism with potential impact for obesity. Cellular Oncology, 44(4), 777-792. DOI: 10.1007/s13402-021-00597-x

Article's DOI: 10.1007/s13402-021-00597-x

Entity: Universitat Rovira i Virgili

Journal publication year: 2021

Publication Type: Journal Publications