DR-nm23 expression affects neuroblastoma cell differentiation, integrin expression, and adhesion characteristics.
METHODS
Nm23 gene family has been associated with metastasis suppression and differentiation. We studied DR-nm23 during neuroblastoma cells differentiation. DR-nm23 expression increased after retinoic acid induction of differentiation in human cell lines SK-N-SH and LAN-5.


RESULTS
In several cell lines, overexpression of DR-nm23 was associated with more differentiated phenotypes. SK-N-SH cells increased vimentin expression, increased deposition of collagen type IV, modulated integrin expression, and underwent growth arrest; the murine neuroblastoma cell line N1E-115 showed neurite outgrowth and a striking enhancement of beta1 integrin expression. Up-regulation of beta1 integrin was specifically responsible for the increase in the adhesion to collagen type I-coated plates. Finally, cells overexpressing DR-nm23 were unable to growth in soft agar.


CONCLUSIONS
In conclusion, DR-nm23 expression is directly involved in differentiation of neuroblastoma cells, and its ability to affects the adhesion to extracellular substrates and to inhibit growth in soft agar suggests an involvement in the metastatic potential of neuroblastoma.
Amendola
R
R
Enea, CR-Casaccia, Section of Toxicology and Biomedical Sciences, Rome, Italy PA. amendola@casaccia.enea.it
Martinez
R
R
Negroni
A
A
Venturelli
D
D
Tanno
B
B
Calabretta
B
B
Raschellà
G
G
D000362:Agar; D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D003470:Culture Media; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016501:Neurites / Q000648:ultrastructure; D009447:Neuroblastoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D009701:Nucleoside-Diphosphate Kinase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics
D003470:Culture Media; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014746:Vimentin; D000362:Agar; D003094:Collagen; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins