Articles producció científica> Medicina i Cirurgia

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

  • Identification data

    Identifier: imarina:9173279
    Authors:
    Benaiges, ECeperuelo-Mallafre, VMadeira, ABosch, RNunez-Roa, CEjarque, MMaymo-Masip, EHuber-Ruano, ILejeune, MVendrell, JFernandez-Veledo, S
    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 m
  • Others:

    Author, as appears in the article.: Benaiges, E; Ceperuelo-Mallafre, V; Madeira, A; Bosch, R; Nunez-Roa, C; Ejarque, M; Maymo-Masip, E; Huber-Ruano, I; Lejeune, M; Vendrell, J; Fernandez-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 Tumor microenvironment Thp-1 cells Survivin Stem cells Phenotype Obesity Neoplasms Humans Ht29 cells Hep g2 cells Hek293 cells Gene expression regulation, neoplastic Gene expression profiling Cells, cultured Cancer Caco-2 cells Birc5 protein, human Adipose-derived stem cells Adipose tissue
    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 elsa.maymo@urv.cat victoria.ceperuelo@urv.cat marylenemarie.lejeune@urv.cat ramon.bosch@urv.cat ester.benaiges@estudiants.urv.cat ester.benaiges@estudiants.urv.cat sonia.fernandez@urv.cat juanjose.vendrell@urv.cat
    Author identifier: 0000-0002-9133-3120 0000-0002-4460-9761 0000-0001-8441-9404 0000-0003-2906-3788 0000-0002-6994-6115
    Record's date: 2024-10-12
    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: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Cellular Oncology. 44 (4): 777-792
    APA: Benaiges, E; Ceperuelo-Mallafre, V; Madeira, A; Bosch, R; Nunez-Roa, C; Ejarque, M; Maymo-Masip, E; Huber-Ruano, I; Lejeune, M; Vendrell, J; Fernandez (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
  • Keywords:

    Cancer Research,Cell Biology,Medicine (Miscellaneous),Molecular Medicine,Oncology,Pathology
    Tumor-associated macrophages
    Tumor microenvironment
    Thp-1 cells
    Survivin
    Stem cells
    Phenotype
    Obesity
    Neoplasms
    Humans
    Ht29 cells
    Hep g2 cells
    Hek293 cells
    Gene expression regulation, neoplastic
    Gene expression profiling
    Cells, cultured
    Cancer
    Caco-2 cells
    Birc5 protein, human
    Adipose-derived stem cells
    Adipose tissue
    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
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