Prostaglandin E2 modulates components of the Wnt signaling system in bone and prostate cancer cells

Xin Hua Liu; Alexander Kirschenbaum; Barrie M. Weinstein; Mone Zaidi; Shen Yao; Alice C. Levine

doi:10.1016/j.bbrc.2010.03.057

Prostaglandin E₂ modulates components of the Wnt signaling system in bone and prostate cancer cells

Xin Hua Liu, Alexander Kirschenbaum, Barrie M. Weinstein, Mone Zaidi, Shen Yao, Alice C. Levine

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Both Wnt signaling and prostaglandin E₂ (PGE₂) play pivotal roles in bone development, remodeling, osteoporosis and prostate cancer (PCa) bone metastases. We investigated the effects of PGE₂ on Wnt signaling in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells. We demonstrate that low dose PGE₂ (0.1 μM) promotes Wnt signaling while higher doses of PGE₂ (1.0-10 μM) inhibit these same parameters in osteoblast-lineage cells. The differential effects of low vs high-dose PGE₂ on pre-osteoblasts may be attributed to dose-dependent modulation of prostaglandin receptor (EP) subtype expression; with lower doses increasing the expression the cAMP-stimulatory EP4 receptor subtype and higher doses increasing the expression of the cAMP-inhibitory EP3 receptor subtype. Moreover, we demonstrate that high expression levels of COX-2 and PGE₂ promote the secretion of Wnt inhibitors from prostate cancer cells. These data demonstrate that there are dose-dependent effects of PGE₂ on Wnt activation in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells which may have clinical implications in the management.

Original language	English
Pages (from-to)	715-720
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	394
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2010.03.057
State	Published - 9 Apr 2010

Keywords

Cyclooxygenase-2
Osteoblasts
Prostaglandin E
Prostate cancer bone metastases
Wnt

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10.1016/j.bbrc.2010.03.057

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@article{21716a5c906948909092266e391e2c8d,

title = "Prostaglandin E2 modulates components of the Wnt signaling system in bone and prostate cancer cells",

abstract = "Both Wnt signaling and prostaglandin E2 (PGE2) play pivotal roles in bone development, remodeling, osteoporosis and prostate cancer (PCa) bone metastases. We investigated the effects of PGE2 on Wnt signaling in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells. We demonstrate that low dose PGE2 (0.1 μM) promotes Wnt signaling while higher doses of PGE2 (1.0-10 μM) inhibit these same parameters in osteoblast-lineage cells. The differential effects of low vs high-dose PGE2 on pre-osteoblasts may be attributed to dose-dependent modulation of prostaglandin receptor (EP) subtype expression; with lower doses increasing the expression the cAMP-stimulatory EP4 receptor subtype and higher doses increasing the expression of the cAMP-inhibitory EP3 receptor subtype. Moreover, we demonstrate that high expression levels of COX-2 and PGE2 promote the secretion of Wnt inhibitors from prostate cancer cells. These data demonstrate that there are dose-dependent effects of PGE2 on Wnt activation in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells which may have clinical implications in the management.",

keywords = "Cyclooxygenase-2, Osteoblasts, Prostaglandin E, Prostate cancer bone metastases, Wnt",

author = "Liu, {Xin Hua} and Alexander Kirschenbaum and Weinstein, {Barrie M.} and Mone Zaidi and Shen Yao and Levine, {Alice C.}",

note = "Funding Information: We thank Dr. Tim Hla (University of Connecticut, Farmingdale, CT) for the COX-2 expression vector and Dr. B. Vogelstein (John Hopkins Oncology Center, Baltimore, MD) for the Tcf-luciferase reporter construct. This work was supported by grants-in-aid from the Department of Defense (DAMD X81XWH-05-1-0166 ) of the US government, the T.J. Martell Foundation for Leukemia, Cancer and Aids Research, and Prostate Action, Inc. (X.H. Liu and A.C. Levine). M. Zaidi acknowledges the support of the National Institutes of Health ( AG23176 and DK80459 ).",

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language = "English",

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T1 - Prostaglandin E2 modulates components of the Wnt signaling system in bone and prostate cancer cells

AU - Liu, Xin Hua

AU - Kirschenbaum, Alexander

AU - Weinstein, Barrie M.

AU - Zaidi, Mone

AU - Yao, Shen

AU - Levine, Alice C.

N1 - Funding Information: We thank Dr. Tim Hla (University of Connecticut, Farmingdale, CT) for the COX-2 expression vector and Dr. B. Vogelstein (John Hopkins Oncology Center, Baltimore, MD) for the Tcf-luciferase reporter construct. This work was supported by grants-in-aid from the Department of Defense (DAMD X81XWH-05-1-0166 ) of the US government, the T.J. Martell Foundation for Leukemia, Cancer and Aids Research, and Prostate Action, Inc. (X.H. Liu and A.C. Levine). M. Zaidi acknowledges the support of the National Institutes of Health ( AG23176 and DK80459 ).

PY - 2010/4/9

Y1 - 2010/4/9

N2 - Both Wnt signaling and prostaglandin E2 (PGE2) play pivotal roles in bone development, remodeling, osteoporosis and prostate cancer (PCa) bone metastases. We investigated the effects of PGE2 on Wnt signaling in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells. We demonstrate that low dose PGE2 (0.1 μM) promotes Wnt signaling while higher doses of PGE2 (1.0-10 μM) inhibit these same parameters in osteoblast-lineage cells. The differential effects of low vs high-dose PGE2 on pre-osteoblasts may be attributed to dose-dependent modulation of prostaglandin receptor (EP) subtype expression; with lower doses increasing the expression the cAMP-stimulatory EP4 receptor subtype and higher doses increasing the expression of the cAMP-inhibitory EP3 receptor subtype. Moreover, we demonstrate that high expression levels of COX-2 and PGE2 promote the secretion of Wnt inhibitors from prostate cancer cells. These data demonstrate that there are dose-dependent effects of PGE2 on Wnt activation in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells which may have clinical implications in the management.

AB - Both Wnt signaling and prostaglandin E2 (PGE2) play pivotal roles in bone development, remodeling, osteoporosis and prostate cancer (PCa) bone metastases. We investigated the effects of PGE2 on Wnt signaling in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells. We demonstrate that low dose PGE2 (0.1 μM) promotes Wnt signaling while higher doses of PGE2 (1.0-10 μM) inhibit these same parameters in osteoblast-lineage cells. The differential effects of low vs high-dose PGE2 on pre-osteoblasts may be attributed to dose-dependent modulation of prostaglandin receptor (EP) subtype expression; with lower doses increasing the expression the cAMP-stimulatory EP4 receptor subtype and higher doses increasing the expression of the cAMP-inhibitory EP3 receptor subtype. Moreover, we demonstrate that high expression levels of COX-2 and PGE2 promote the secretion of Wnt inhibitors from prostate cancer cells. These data demonstrate that there are dose-dependent effects of PGE2 on Wnt activation in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells which may have clinical implications in the management.

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KW - Osteoblasts

KW - Prostaglandin E

KW - Prostate cancer bone metastases

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