title: Human a-L-fucosidase-1 attenuates the invasive properties of thyroid cancer.
abstract: 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.
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Via Sergio Pansini, 5, Naples, Italy.|Istituto Superiore di Oncologia, Via Sergio Pansini, 5, Naples and Via Balbi 5, Genoa, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Vecchio
authors.affiliation: IRCCS SDN, Naples, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Parascandolo
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Via Sergio Pansini, 5, Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Allocca
authors.affiliation: Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Ugolini
authors.affiliation: Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, University of Pisa, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.affiliation: Institute of Biosciences and Bioresources (IBBR), National Research Council of Italy (CNR), Via P. Castellino, 111, Naples, Italy.|Department of Biology, University of Naples "Federico II", Complesso Universitario di Monte S. Angelo, Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Moracci
authors.affiliation: Institute of Biosciences and Bioresources (IBBR), National Research Council of Italy (CNR), Via P. Castellino, 111, Naples, Italy.|Department of Biology, University of Naples "Federico II", Complesso Universitario di Monte S. Angelo, Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Strazzulli
authors.affiliation: Institute of Biosciences and Bioresources (IBBR), National Research Council of Italy (CNR), Via P. Castellino, 111, Naples, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Cobucci-Ponzano
authors.affiliation: IRCCS SDN, Naples, Italy.
authors.forename: Mikko O
authors.initials: MO
authors.lastname: Laukkanen
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" (IEOS), CNR, Naples, Italy.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Castellone
authors.affiliation: Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Tsuchida
mesh_terms: D000708:Anaplasia; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D019040:E-Selectin / Q000378:metabolism; D004789:Enzyme Activation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011485:Protein Binding; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D005644:alpha-L-Fucosidase / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019040:E-Selectin; D005644:alpha-L-Fucosidase
keywords: fucosidase; glycosylation; metastasis; thyroid carcinoma