Open AccessExtracellular NM23 protein promotes the growth and survival of primary cultured human acute myelogenous leukemia cells
Author(s) -
OkabeKado Junko,
Kasukabe Takashi,
Honma Yoshio,
Kobayashi Hirofumi,
Maseki Nobuo,
Kaneko Yasuhiko
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01276.x
Subject(s) - extracellular , leukemia , mapk/erk pathway , cytokine , cancer research , signal transduction , biology , in vitro , intracellular , immunology , microbiology and biotechnology , biochemistry
An elevated serum level of NM23‐H1 protein is found in acute myelogenous leukemia (AML), and predicts a poor treatment outcome in AML patients. To investigate the potential pathological link between the elevated serum level of this protein and poor prognosis, we examined the extracellular effects of recombinant NM23‐H1 protein on the in vitro growth and survival of primary cultured AML cells at concentrations equivalent to the levels found in the serum of AML patients. Extracellular NM23‐H1 protein promoted the in vitro growth and survival of AML cells and this activity was associated with the cytokine production and activation of the MAPK and signal transducers and activators of transcription signaling pathways. Inhibitors specific to MAPK signaling pathways inhibited the growth‐ and survival‐promoting activity of NM23‐H1. These findings indicate the novel biological action of extracellular NM23‐H1 and its association with poor prognosis, and suggest an important role for extracellular NM23‐H1 in the malignant progression of leukemia and a potential therapeutic target for these malignancies. ( Cancer Sci 2009; 100: 1885–1894)