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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-7-28
pubmed:abstractText
Nucleoside diphosphate kinase A (NDPK-A), encoded by the nm23-H1 gene, acts as a metastasis suppressor in certain human tumors such as breast carcinoma. However, evidence also points to NDPK-A functioning as a metastasis promoter in other human tumors including neuroblastoma. In fact, amplification and overexpression of nm23-H1 as well as S120G mutation of NDPK-A (NDPK-A(S120G)) have been detected in 14% to 30% of patients with advanced stages of neuroblastoma. To test whether NDPK-A promotes neuroblastoma metastasis, we established stable transfectants and an orthotopic xenograft animal model from the human neuroblastoma NB69 cell line. We demonstrate that overexpressed NDPK-A or NDPK-A(S120G) increased both incidence and colonization of neuroblastoma metastasis in animal lungs without significantly affecting primary tumor development. In vitro, these metastasis-associated NDPK-A aberrations abrogated retinoic acid-induced neuronal differentiation while increasing cloning efficiency, cell survival, and colony formation of NB69 derivatives. Furthermore, NDPK-A(S120G) reduced cell adhesion and increased cell migration. Compared with its wild-type, NDPK-A(S120G) appears more effective in promoting neuroblastoma metastasis. Our results provide the first evidence that NDPK-A behaves as a metastasis promoter at least in human neuroblastoma derived from NB69 cells. The findings not only suggest a prognostic value of NDPK-A in neuroblastoma patients but also caution NDPK-A-targeted treatment for patients with different tumor types.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
387-94
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15280446-Animals, pubmed-meshheading:15280446-Cell Adhesion, pubmed-meshheading:15280446-Cell Differentiation, pubmed-meshheading:15280446-Cell Line, Tumor, pubmed-meshheading:15280446-Cell Movement, pubmed-meshheading:15280446-Cell Proliferation, pubmed-meshheading:15280446-Cell Survival, pubmed-meshheading:15280446-Clone Cells, pubmed-meshheading:15280446-Disease Models, Animal, pubmed-meshheading:15280446-Humans, pubmed-meshheading:15280446-Lung Neoplasms, pubmed-meshheading:15280446-Mice, pubmed-meshheading:15280446-Mice, SCID, pubmed-meshheading:15280446-Mutation, pubmed-meshheading:15280446-NM23 Nucleoside Diphosphate Kinases, pubmed-meshheading:15280446-Neoplasm Metastasis, pubmed-meshheading:15280446-Neoplasm Transplantation, pubmed-meshheading:15280446-Neuroblastoma, pubmed-meshheading:15280446-Nucleoside-Diphosphate Kinase, pubmed-meshheading:15280446-Transfection
pubmed:year
2004
pubmed:articleTitle
Nucleoside diphosphate kinase A/nm23-H1 promotes metastasis of NB69-derived human neuroblastoma.
pubmed:affiliation
Department of Medicine, University of California at San Diego, 4028 Basic Science Building, 9500 Gilman Drive, La Jolla, CA 92093-0688, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.