1. NGAL Controls the Metastatic Potential of Anaplastic Thyroid Carcinoma Cells
- Author
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Stefano Mellone, Fortunato Moscato, Domenico Somma, Luca Sanguigno, Vincenzo Volpe, Francesco Pacifico, Antonio Leonardi, Paola Mastrovito, Zelinda Raia, Volpe, V., Raia, Z., Sanguigno, L., Somma, Domenico, Mastrovito, Paola, Moscato, F., Mellone, S., Leonardi, Antonio, and Pacifico, F.
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Mice, Nude ,Context (language use) ,Thyroid Carcinoma, Anaplastic ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Thyroid carcinoma ,Mice ,Endocrinology ,Lipocalin-2 ,Gentamicin protection assay ,Proto-Oncogene Proteins ,Internal medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Medicine ,Neoplasm Invasiveness ,Thyroid Neoplasms ,Neoplasm Metastasis ,RNA, Small Interfering ,Thyroid cancer ,Matrigel ,business.industry ,Biochemistry (medical) ,NF-kappa B ,medicine.disease ,Lipocalins ,Gene Expression Regulation, Neoplastic ,HEK293 Cells ,Matrix Metalloproteinase 9 ,Cell culture ,Gene Knockdown Techniques ,Cancer cell ,Ectopic expression ,business ,Acute-Phase Proteins - Abstract
Context: We have previously identified neutrophil gelatinase-associated lipocalin (NGAL) as one of the genes mediating the oncogenic activity of nuclear factor-?B in human anaplastic thyroid carcinomas (ATCs). Objectives: To further investigate the role of NGAL in thyroid cancer, we established NGAL knocked-down and NGAL overexpressing ATC cell lines. Results: We found that the ability of NGAL knocked-down cells to degrade Matrigel in a transwell invasion assay and to form lung metastasis in nude mice was decreased. Because NGAL binds matrix metalloproteinase-9 (MMP-9), to form a macromolecular complex involved in the regulation of metastatic spread of cancer cells and given the strong expression of both genes in tissue specimens from human ATCs, we analyzed the MMP-9 enzymatic activity in NGAL-null ATC cells. Enzymatic immunoassays show that MMP-9 activity is reduced in NGAL-null ATC cells, even if its expression is not affected by NGAL inhibition. Ectopic expression of NGAL in an ATC cell line not expressing NGAL determines an increase of its metastatic property. The use of a mutated form of NGAL, unable to bind MMP-9, has no positive effect on the invasive potential of ATC cells and does not improve the MMP-9 enzymatic activity. Conclusions: Our results indicate NGAL as a novel target of nuclear factor-?B prometastatic activity in thyroid cancer through enhancement of MMP-9 enzymatic activity.
- Published
- 2013
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