title: All trans-retinoic acid abrogates the pro-tumorigenic phenotype of prostate cancer tumor-associated macrophages.
abstract: Tumor-associated macrophages (TAMs) are a prominent cell type of the tumor stroma and stimulate malignant cell growth, survival and metastasis. The present manuscript demonstrates that prostate cancer cell-derived factors induce a pro-tumoral TAM-like phenotype characterized by increased proliferation and increased expression of pro-angiogenic, immunosuppressive and pro-metastatic factors. These effects were abrogated by all trans-retinoic acid (ATRA), a clinically available molecule with known immune-modulating properties. Furthermore, ATRA inhibited the cancer cell-stimulated proliferation of the pro-tumoral macrophages and restored their cytotoxic capacity towards prostate cancer cells. These findings suggest the use of ATRA as an immunomodulating agent to block the activity of prostate cancer TAMs.
authors.affiliation: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden; Section of Orthopaedics, Department of Molecular Medicine and Surgery, Karolinska Institute and Department of Orthopaedics, Karolinska University Hospital, Stockholm, Sweden. Electronic address: panagiotis.tsagkozis@karolinska.se.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsagozis
authors.affiliation: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Augsten
authors.affiliation: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden; Roche Glycart AG, Wagistrasse 18, CH-8952 Schlieren, Switzerland.
authors.forename: Pavel
authors.initials: P
authors.lastname: Pisa
mesh_terms: D063646:Carcinogenesis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007165:Immunosuppression Therapy; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D016207:Cytokines; D017346:Protein Serine-Threonine Kinases; D014212:Tretinoin; D000097782:NF-kappaB-Inducing Kinase
keywords: Cancer; Macrophage; Prostate; Retinoic