Human a-L-fucosidase-1 attenuates the invasive properties of thyroid cancer
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Giancarlo Vecchio1,2,*, Alessia Parascandolo3,*, Chiara Allocca1, Clara Ugolini4, Fulvio Basolo5, Marco Moracci6,7, Andrea Strazzulli6,7, Beatrice Cobucci-Ponzano6, Mikko O. Laukkanen3, Maria Domenica Castellone8, Nobuo Tsuchida9
1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Via Sergio Pansini, 5, Naples, Italy
2Istituto Superiore di Oncologia, Via Sergio Pansini, 5, Naples and Via Balbi 5, Genoa, Italy
3IRCCS SDN, Naples, Italy
4Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
5Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, University of Pisa, Italy
6Institute of Biosciences and Bioresources (IBBR), National Research Council of Italy (CNR), Via P. Castellino, 111, Naples, Italy
7Department of Biology, University of Naples “Federico II”, Complesso Universitario di Monte S. Angelo, Naples, Italy
8Istituto di Endocrinologia ed Oncologia Sperimentale “G. Salvatore” (IEOS), CNR, Naples, Italy
9Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University, Tokyo, Japan
*These authors have contributed equally to this work
Maria Domenica Castellone, email: email@example.com
Nobuo Tsuchida, email: firstname.lastname@example.org
Keywords: glycosylation, fucosidase, thyroid carcinoma, metastasis
Received: November 24, 2016 Accepted: January 24, 2017 Published: February 23, 2017
Glycans containing α-L-fucose participate in diverse interactions between cells and extracellular matrix. High glycan expression on cell surface is often associated with neoplastic progression. The lysosomal exoenzyme, α-L-fucosidase-1 (FUCA-1) removes fucose residues from glycans. The FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors. However, the role of FUCA-1 in tumor progression remains unclear. It is speculated that its inactivation perturbs glycosylation of proteins involved in cell adhesion and promotes cancer. FUCA-1 expression of various thyroid normal and cancer tissues assayed by immunohistochemical (IHC) staining was high in normal thyroids and papillary thyroid carcinomas (PTC), whereas it progressively decreased in poorly differentiated, metastatic and anaplastic thyroid carcinomas (ATC). FUCA-1 mRNA expression from tissue samples and cell lines and protein expression levels and enzyme activity in thyroid cancer cell lines paralleled those of IHC staining. Furthermore, ATC-derived 8505C cells adhesion to human E-selectin and HUVEC cells was inhibited by bovine α-L-fucosidase or Lewis antigens, thus pointing to an essential role of fucose residues in the adhesive phenotype of this cancer cell line. Finally, 8505C cells transfected with a FUCA-1 containing plasmid displayed a less invasive phenotype versus the parental 8505C. These results demonstrate that FUCA-1 is down-regulated in ATC compared to PTC and normal thyroid tissues and cell lines. As shown for other human cancers, the down-regulation of FUCA-1 correlates with increased aggressiveness of the cancer type. This is the first report indicating that the down-regulation of FUCA-1 is related to the increased aggressiveness of thyroid cancer.
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