Activated Leukocyte Cell Adhesion Molecule Expression and Shedding in Thyroid Tumors

Autor: Luca Da Riva, Marina Fabbi, Italia Bongarzone, Silvana Pilotti, Piera Mondellini, Silvano Ferrini, Marco A. Pierotti, Silvana Canevari, Francesca Miccichè
Rok vydání: 2011
Předmět:
Proteomics
Pathology
lcsh:Medicine
Biochemistry
Thyroid
Papillary Carcinoma
Cell Movement
Molecular Cell Biology
Protein Isoforms
Epidermal growth factor receptor
Thyroid
Medullary Carcinoma
RNA
Small Interfering
lcsh:Science
Endocrine Tumors
Thyroid cancer
Multidisciplinary
Ionomycin
Activated-Leukocyte Cell Adhesion Molecule
Cell migration
Thyroid
Anaplastic Carcinoma
Head and Neck Tumors
Extracellular Matrix
Gene Expression Regulation
Neoplastic
Protein Transport
Oncology
Ectodomain
Thyroid Cancer
Papillary
Medicine
Tetradecanoylphorbol Acetate
Research Article
Biotechnology
medicine.medical_specialty
Biology
Cell Line
Tumor
Cell Adhesion
Biomarkers
Tumor
medicine
Humans
Thyroid Neoplasms
Cell adhesion
Extracellular Matrix Adhesions
ALCAM
Ionophores
lcsh:R
Carcinoma
Cancers and Neoplasms
Thyroid Lymphoma
medicine.disease
Carcinoma
Papillary
Cell culture
Thyroid
Follicular Carcinoma
Cancer research
biology.protein
lcsh:Q
Zdroj: PLoS ONE
PLoS ONE, Vol 6, Iss 2, p e17141 (2011)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0017141
Popis: Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. Here we documented high levels of ALCAM expression in human thyroid tumors and cell lines. Through proteomic characterization of ALCAM expression in the human papillary thyroid carcinoma cell line TPC-1, we identified the presence of a full-length membrane-associated isoform in cell lysate and of soluble ALCAM isoforms in conditioned medium. This finding is consistent with proteolytically shed ALCAM ectodomains. Nonspecific agents, such as phorbol myristate acetate (PMA) or ionomycin, provoked increased ectodomain shedding. Epidermal growth factor receptor stimulation also enhanced ALCAM secretion through an ADAM17/TACE-dependent pathway. ADAM17/TACE was expressed in the TPC-1 cell line, and ADAM17/TACE silencing by specific small interfering RNAs reduced ALCAM shedding. In addition, the CGS27023A inhibitor of ADAM17/TACE function reduced ALCAM release in a dose-dependent manner and inhibited cell migration in a wound-healing assay. We also provide evidence for the existence of novel O-glycosylated forms and of a novel 60-kDa soluble form of ALCAM, which is particularly abundant following cell stimulation by PMA. ALCAM expression in papillary and medullary thyroid cancer specimens and in the surrounding non-tumoral component was studied by western blot and immunohistochemistry, with results demonstrating that tumor cells overexpress ALCAM. These findings strongly suggest the possibility that ALCAM may have an important role in thyroid tumor biology.
Databáze: OpenAIRE
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