title: Extracellular Superoxide Dismutase Expression in Papillary Thyroid Cancer Mesenchymal Stem/Stromal Cells Modulates Cancer Cell Growth and Migration.
abstract: Tumor stroma-secreted growth factors, cytokines, and reactive oxygen species (ROS) influence tumor development from early stages to the metastasis phase. Previous studies have demonstrated downregulation of ROS-producing extracellular superoxide dismutase (SOD3) in thyroid cancer cell lines although according to recent data, the expression of SOD3 at physiological levels stimulates normal and cancer cell proliferation. Therefore, to analyze the expression of SOD3 in tumor stroma, we characterized stromal cells from the thyroid. We report mutually exclusive desmoplasia and inflammation in papillary and follicular thyroid cancers and the presence of multipotent mesenchymal stem/stromal cells (MSCs) in non-carcinogenic thyroids and papillary thyroid cancer (PTC). The phenotypic and differentiation characteristics of Thyroid MSCs and PTC MSCs were comparable with bone marrow MSCs. A molecular level analysis showed increased FIBROBLAST ACTIVATING PROTEIN, COLLAGEN 1 TYPE A1, TENASCIN, and SOD3 expression in PTC MSCs compared to Thyroid MSCs, suggesting the presence of MSCs with a fibrotic fingerprint in papillary thyroid cancer tumors and the autocrine-paracrine conversion of SOD3 expression, which was enhanced by cancer cells. Stromal SOD3 had a stimulatory effect on cancer cell growth and an inhibitory effect on cancer cell migration, thus indicating that SOD3 might be a novel player in thyroid tumor stroma.
authors.affiliation: IRCCS SDN, Naples 80143, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Parascandolo
authors.affiliation: Department of Experimental and Clinical Neurosciences, University of Palermo, 90133, Italy.|Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rappa
authors.affiliation: Department of Experimental and Clinical Neurosciences, University of Palermo, 90133, Italy.|Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Wisconsin 53792, USA.
authors.forename: Jaehyup
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Wisconsin 53792, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Cantu
authors.affiliation: Department of Surgery, University of Alabama, Birmingham, AL, USA.
authors.forename: Herbert
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS "Casa Sollievo della Sofferenza", S. Giovanni Rotondo (FG) 71013, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mazzoccoli
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Wisconsin 53792, USA.|University of Wisconsin Carbone Cancer Center, Madison, Wisconsin 53792, USA.
authors.forename: Peiman
authors.initials: P
authors.lastname: Hematti
authors.affiliation: Institute of Experimental Endocrinology and Oncology (CNR), 80014 Naples, Italy.|Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80014 Naples, Italy.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Castellone
authors.affiliation: IRCCS SDN, Naples 80143, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Salvatore
authors.affiliation: IRCCS SDN, Naples 80143, Italy.
authors.forename: Mikko O
authors.initials: MO
authors.lastname: Laukkanen
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000201:enzymology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005110:Extracellular Space / Q000201:enzymology*; D005355:Fibrosis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D019899:Paracrine Communication; D010641:Phenotype; D013482:Superoxide Dismutase / Q000378:metabolism*; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C441642:SOD3 protein, human; D013482:Superoxide Dismutase