Nucleoside diphosphate kinase A/nm23-H1 promotes metastasis of NB69-derived human neuroblastoma.

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.
AuthorsMalin A E Almgren, K Cecilia E Henriksson, Jennifer Fujimoto, Christina L Chang
JournalMolecular cancer research : MCR (Mol Cancer Res) Vol. 2 Issue 7 Pg. 387-94 (Jul 2004) ISSN: 1541-7786 [Print] United States
PMID15280446 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • NM23 Nucleoside Diphosphate Kinases
  • NME1 protein, human
  • Nme1 protein, mouse
  • Nucleoside-Diphosphate Kinase
  • Animals
  • Cell Adhesion
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Clone Cells (metabolism, pathology)
  • Disease Models, Animal
  • Humans
  • Lung Neoplasms (secondary)
  • Mice
  • Mice, SCID
  • Mutation
  • NM23 Nucleoside Diphosphate Kinases
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neuroblastoma (enzymology, metabolism, pathology)
  • Nucleoside-Diphosphate Kinase (genetics, metabolism)
  • Transfection

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