title: NGAL controls the metastatic potential of anaplastic thyroid carcinoma cells.
abstract: BACKGROUND
  We have previously identified neutrophil gelatinase-associated lipocalin (NGAL) as one of the genes mediating the oncogenic activity of nuclear factor-κB in human anaplastic thyroid carcinomas (ATCs).
  
  
  OBJECTIVE
  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-κB prometastatic activity in thyroid cancer through enhancement of MMP-9 enzymatic activity.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Federico II University of Naples, 80131 Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Volpe
authors.forename: Zelinda
authors.initials: Z
authors.lastname: Raia
authors.forename: Luca
authors.initials: L
authors.lastname: Sanguigno
authors.forename: Domenico
authors.initials: D
authors.lastname: Somma
authors.forename: Paola
authors.initials: P
authors.lastname: Mastrovito
authors.forename: Fortunato
authors.initials: F
authors.lastname: Moscato
authors.forename: Stefano
authors.initials: S
authors.lastname: Mellone
authors.forename: Antonio
authors.initials: A
authors.lastname: Leonardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Pacifico
mesh_terms: D000209:Acute-Phase Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D020780:Matrix Metalloproteinase 9