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Nitric oxide stimulates migration of human endothelial and prostate cancer cells through up‐regulation of pleiotrophin expression and its receptor protein tyrosine phosphatase β/ζ
Author(s) -
Polytarchou Christos,
Hatziapostolou Maria,
Poimenidi Evangelia,
Mikelis Constantinos,
Papadopoulou Ariadni,
Parthymou Anastasia,
Papadimitriou Evangelia
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24084
Subject(s) - pleiotrophin , cyclopamine , chemistry , mapk/erk pathway , cell migration , microbiology and biotechnology , cancer research , biology , signal transduction , receptor , growth factor , cell , biochemistry , hedgehog signaling pathway
Pleiotrophin (PTN) is a secreted growth factor involved in angiogenesis and tumor growth. We have recently shown that low concentrations of hydrogen peroxide (HP) stimulate PTN expression, through activation of the transcription factor AP‐1. In the present work, we studied the possible involvement of endothelial nitric oxide synthase (eNOS) and the role of nitric oxide (NO) in the regulation of PTN expression, as well as involvement of the latter in the NO‐induced human endothelial and prostate cancer cell migration. Inhibition of eNOS or the downstream effector soluble guanylate cyclase (sGC) completely suppressed HP‐induced AP‐1 activities that lead to PTN expression and cell migration. The NO donor sodium nitroprusside (SNP) through activation of sGC significantly and concentration‐dependently increased expression of PTN, through transcriptional activation of the corresponding gene. Moreover, SNP had no effect on the migration of stably transfected prostate cancer cells that do not express PTN and knockdown of PTN receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ) completely abolished SNP‐induced cell migration. NO added exogenously or produced endogenously by low concentrations of HP through stimulation of sGC activates extracellular signal‐regulated kinase[1/2] (ERK[1/2]) and leads to PTN expression and cell migration. On the other hand, p38, which also intervenes in the up‐regulation of PTN expression by low concentrations of HP, seems to act upstream of eNOS and does not intervene in the SNP‐induced PTN expression and cell migration. The above data suggest that PTN through its receptor RPTPβ/ζ is a mediator of the stimulatory effects of eNOS/NO on human endothelial and prostate cancer cell migration. © 2008 Wiley‐Liss, Inc.