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Title: High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation

Abstract

Although most of pharmacological therapies for cancer utilize the apoptotic machinery of the cells, the available anti-cancer drugs are limited due to the ability of prostate cancer cells to escape from the anti-cancer drug-induced apoptosis. A human prostate cancer cell line PC3 is resistant to camptothecin (CPT). To elucidate the mechanism of this resistance, we have examined the involvement of sphingosine kinase (SPHK) and sphingosine 1-phosphate (S1P) receptor in CPT-resistant PC3 and -sensitive LNCaP cells. PC3 cells exhibited higher activity accompanied with higher expression levels of protein and mRNA of SPHK1, and also elevated expression of S1P receptors, S1P{sub 1} and S1P{sub 3}, as compared with those of LNCaP cells. The knockdown of SPHK1 by small interfering RNA and inhibition of S1P receptor signaling by pertussis toxin in PC3 cells induced significant inhibition of cell growth, suggesting implication of SPHK1 and S1P receptors in cell proliferation in PC3 cells. Furthermore, the treatment of PC3 cells with CPT was found to induce up-regulation of the SPHK1/S1P signaling by induction of both SPHK1 enzyme and S1P{sub 1}/S1P{sub 3} receptors. These findings strongly suggest that high expression and up-regulation of SPHK1 and S1P receptors protect PC3 cells from the apoptosis induced by CPT.

Authors:
 [1];  [2];  [3];  [3];  [4];  [5];  [4];  [3]
  1. Gifu International Institute of Biotechnology, Kakamigahara 504-0838 (Japan). E-mail: yakao@giib.or.jp
  2. Department of Cell Signaling, Gifu University Graduate School of Medicine, Gifu 501-1194 (Japan)
  3. Gifu International Institute of Biotechnology, Kakamigahara 504-0838 (Japan)
  4. Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812 (Japan)
  5. Nagoya University Graduate School of Medicine, Nagoya University School of Health Sciences, Nagoya 461-8673 (Japan)
Publication Date:
OSTI Identifier:
20798909
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 342; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2006.02.070; PII: S0006-291X(06)00366-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CARCINOMAS; CELL PROLIFERATION; CHEMOTHERAPY; DRUGS; ENZYMES; GENE REGULATION; INHIBITION; PHOSPHATES; PROSTATE; RECEPTORS; RNA; TOXINS

Citation Formats

Akao, Yukihiro, Banno, Yoshiko, Nakagawa, Yoshihito, Hasegawa, Nobuko, Kim, Tack-Joong, Murate, Takashi, Igarashi, Yasuyuki, and Nozawa, Yoshinori. High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.02.070.
Akao, Yukihiro, Banno, Yoshiko, Nakagawa, Yoshihito, Hasegawa, Nobuko, Kim, Tack-Joong, Murate, Takashi, Igarashi, Yasuyuki, & Nozawa, Yoshinori. High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation. United States. doi:10.1016/j.bbrc.2006.02.070.
Akao, Yukihiro, Banno, Yoshiko, Nakagawa, Yoshihito, Hasegawa, Nobuko, Kim, Tack-Joong, Murate, Takashi, Igarashi, Yasuyuki, and Nozawa, Yoshinori. Fri . "High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation". United States. doi:10.1016/j.bbrc.2006.02.070.
@article{osti_20798909,
title = {High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation},
author = {Akao, Yukihiro and Banno, Yoshiko and Nakagawa, Yoshihito and Hasegawa, Nobuko and Kim, Tack-Joong and Murate, Takashi and Igarashi, Yasuyuki and Nozawa, Yoshinori},
abstractNote = {Although most of pharmacological therapies for cancer utilize the apoptotic machinery of the cells, the available anti-cancer drugs are limited due to the ability of prostate cancer cells to escape from the anti-cancer drug-induced apoptosis. A human prostate cancer cell line PC3 is resistant to camptothecin (CPT). To elucidate the mechanism of this resistance, we have examined the involvement of sphingosine kinase (SPHK) and sphingosine 1-phosphate (S1P) receptor in CPT-resistant PC3 and -sensitive LNCaP cells. PC3 cells exhibited higher activity accompanied with higher expression levels of protein and mRNA of SPHK1, and also elevated expression of S1P receptors, S1P{sub 1} and S1P{sub 3}, as compared with those of LNCaP cells. The knockdown of SPHK1 by small interfering RNA and inhibition of S1P receptor signaling by pertussis toxin in PC3 cells induced significant inhibition of cell growth, suggesting implication of SPHK1 and S1P receptors in cell proliferation in PC3 cells. Furthermore, the treatment of PC3 cells with CPT was found to induce up-regulation of the SPHK1/S1P signaling by induction of both SPHK1 enzyme and S1P{sub 1}/S1P{sub 3} receptors. These findings strongly suggest that high expression and up-regulation of SPHK1 and S1P receptors protect PC3 cells from the apoptosis induced by CPT.},
doi = {10.1016/j.bbrc.2006.02.070},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 342,
place = {United States},
year = {Fri Apr 21 00:00:00 EDT 2006},
month = {Fri Apr 21 00:00:00 EDT 2006}
}
  • Sphingosine-1-phosphate (S1P) is a bioactive lipid that signals through a family of five G-protein-coupled receptors, termed S1P{sub 1-5}. S1P stimulates growth and invasiveness of glioma cells, and high expression levels of the enzyme that forms S1P, sphingosine kinase-1, correlate with short survival of glioma patients. In this study we examined the mechanism of S1P stimulation of glioma cell proliferation and invasion by either overexpressing or knocking down, by RNA interference, S1P receptor expression in glioma cell lines. S1P{sub 1}, S1P{sub 2} and S1P{sub 3} all contribute positively to S1P-stimulated glioma cell proliferation, with S1P{sub 1} being the major contributor. Stimulationmore » of glioma cell proliferation by these receptors correlated with activation of ERK MAP kinase. S1P{sub 5} blocks glioma cell proliferation, and inhibits ERK activation. S1P{sub 1} and S1P{sub 3} enhance glioma cell migration and invasion. S1P{sub 2} inhibits migration through Rho activation, Rho kinase signaling and stress fiber formation, but unexpectedly, enhances glioma cell invasiveness by stimulating cell adhesion. S1P{sub 2} also potently enhances expression of the matricellular protein CCN1/Cyr61, which has been implicated in tumor cell adhesion, and invasion as well as tumor angiogenesis. A neutralizing antibody to CCN1 blocked S1P{sub 2}-stimulated glioma invasion. Thus, while S1P{sub 2} decreases glioma cell motility, it may enhance invasion through induction of proteins that modulate glioma cell interaction with the extracellular matrix.« less
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