Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma

Autor: Nadège Corradini, Clotilde Dumars, Dominique Heymann, Aurelie Gaultier, Marie-Françoise Heymann, Rachel Lanel, Jean-Michel Ngyuen, François Gouin
Přispěvatelé: Centre hospitalier universitaire de Nantes (CHU Nantes), Equipe LIGUE Nationale Contre le Cancer 2012, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Léon-Bérard : Centre de lutte contre le cancer de Lyon et Rhône-Alpes, European Associated Laboratory [Sheffield, UK] (Sarcoma Research Unit), The University of Sheffield [Sheffield, U.K.], This study was supported by the Ligue Nationale Contre le Cancer (Equipe LIGUE 2012) and the Bone Cancer Research Trust, UK (research project number 144681)., Heymann, Dominique
Rok vydání: 2016
Předmět:
0301 basic medicine
Pathology
Cell Plasticity
Nitric Oxide Synthase Type II
Metastasis
0302 clinical medicine
Risk Factors
Odds Ratio
Tumor Microenvironment
Child
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Aged
80 and over
[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
Tissue microarray
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Middle Aged
Immunohistochemistry
3. Good health
Phenotype
Treatment Outcome
Oncology
[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
tumour associated macrophage
030220 oncology & carcinogenesis
Osteosarcoma
Sarcoma
Adult
medicine.medical_specialty
Adolescent
Macrophage polarization
Antigens
Differentiation
Myelomonocytic
[SDV.CAN]Life Sciences [q-bio]/Cancer
Bone Neoplasms
Receptors
Cell Surface
CD146 Antigen
03 medical and health sciences
Young Adult
[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics
Osteoprotegerin
[SDV.CAN] Life Sciences [q-bio]/Cancer
Antigens
CD
osteosarcoma
Pathology Section
medicine
Biomarkers
Tumor
Humans
Aged
Proportional Hazards Models
Tumor microenvironment
[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics
business.industry
Macrophages
RANK Ligand
medicine.disease
Research Paper: Pathology
030104 developmental biology
Logistic Models
Tissue Array Analysis
osteoprotegerin
Multivariate Analysis
Cancer research
Osteopontin
business
CD163
Zdroj: Oncotarget
Oncotarget, 2016, 7 (48), pp.78343-78354. ⟨10.18632/oncotarget.13055⟩
Oncotarget, Impact journals, 2016, 7 (48), pp.78343-78354. ⟨10.18632/oncotarget.13055⟩
ISSN: 1949-2553
0032-0889
DOI: 10.18632/oncotarget.13055⟩
Popis: // Clotilde Dumars 1,2,3 , Jean-Michel Ngyuen 2,3 , Aurelie Gaultier 3 , Rachel Lanel 1,2 , Nadege Corradini 4 , Francois Gouin 1,2,3 , Dominique Heymann 1,2,3,5 and Marie-Francoise Heymann 1,2,3,5 1 INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer, Nantes, France 2 Universite de Nantes, Nantes atlantique universites, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumors, Nantes, France 3 CHU de Nantes, Nantes University Hospital, France 4 Centre de Lutte Contre le Cancer, Leon Berard, Lyon, France 5 INSERM, European Associated Laboratory “Sarcoma Research Unit”, Department of Oncology and Metabolism, University of Sheffield, Medical School, Sheffield, UK Correspondence to: Marie-Francoise Heymann, email: // Dominique Heymann, email: // Keywords : osteosarcoma, tumour associated macrophage, osteoprotegerin, Pathology Section Received : September 24, 2016 Accepted : October 27, 2016 Published : November 13, 2016 Abstract Osteosarcoma (OS) is the most common bone sarcoma in adolescents, and has poor prognosis. A vicious cycle is established between OS cells and their microenvironment in order to facilitate the tumor growth and cell spreading. The present work aims to better characterize the tumor microenvironment in OS in order to identify new therapeutic targets relating to metastatic process. Tissue microarrays of pre-chemotherapy OS biopsies were used for characterizing the tumor niche by immunohistochemistry. Parameters studies included: immune cells (M1, M2-subtypes of tumor-associated macrophages (TAM); T, B lymphocytes; mast cells), vascularization (endothelial, perivascular cells), OPG, RANKL, and mitotic index. Two groups of patients were defined, 22 localized OS (OS Meta-) and 28 metastatic OS (OS Meta+). The OS Meta- group was characterized by a higher infiltration of INOS + M1-polarizedmacrophages and upregulated OPG immunostaining. OS Meta+ tumors showed a significant increase in CD146 + cells. INOS + M1-macrophages were correlated with OPG staining, and negatively with the presence of metastases. CD163 + M2-macrophages were positively correlated with CD146 + cells. In multivariate analysis, INOS and OPG were predictive factors for metastasis. An older age, non-metastatic tumor, good response to chemotherapy, and higher macrophage infiltration were significantly associated with better overall survival. TAMs are associated with better overall survival and a dysregulation of M1/M2 polarized-macrophages in favor of M1 subtype was observed in non-metastatic OS.
Databáze: OpenAIRE
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