TY - JOUR
T1 - Extracellular Superoxide Dismutase Expression in Papillary Thyroid Cancer Mesenchymal Stem/Stromal Cells Modulates Cancer Cell Growth and Migration
AU - Parascandolo, Alessia
AU - Rappa, Francesca
AU - Cappello, Francesco
AU - Kim, Jaehyup
AU - Cantu, David A.
AU - Chen, Herbert
AU - Mazzoccoli, Gianluigi
AU - Hematti, Peiman
AU - Castellone, Maria Domenica
AU - Salvatore, Marco
AU - Laukkanen, Mikko O.
N1 - Publisher Copyright:
© The Author(s) 2017.
PY - 2017/2/20
Y1 - 2017/2/20
N2 - 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.
AB - 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.
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U2 - 10.1038/srep41416
DO - 10.1038/srep41416
M3 - Article
C2 - 28216675
AN - SCOPUS:85013347187
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
M1 - 41416
ER -