Heparin affin regulatory peptide is a key player in prostate cancer cell growth and angiogenicity

Hatziapostolou, Maria; Delbé, Jean; Katsoris, Panagiotis; Polytarchou, Christos; Courty, José; Papadimitriou, Evangelia

doi:10.1002/pros.20270

Cited by 40 publications

(76 citation statements)

References 29 publications

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“…However, tumor growth eventually recur due to a transition from an androgen-dependent to an androgen-independent state, leading to a highly metastatic disease that eventually kills the patient (41). In addition to androgens, growth factors, including pleiotrophin, have been shown to play a key role in the development and progression of the disease (11,(42)(43). The present study demonstrates a role for pleiotrophin receptors, RPTP␤/ and syndecan-3, in prostate cancer metastasis and shed light on the molecular mechanism involved.…”

Section: Discussionmentioning

confidence: 99%

Loss of Receptor Protein Tyrosine Phosphatase β/ζ (RPTPβ/ζ) Promotes Prostate Cancer Metastasis

Diamantopoulou

Kitsou

Ménashi

et al. 2012

Journal of Biological Chemistry

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Background:The role of pleiotrophin and its receptors RPTP␤/ and Syndecan-3 during tumor metastasis remains unknown. Results: RPTP␤/ knockdown initiates EMT, promotes pleiotrophin-mediated migration and attachment through Syndecan-3 and induces in vivo metastasis. Conclusion: RPTP␤/ plays a suppressor-like role in prostate cancer metastasis. Significance: Boosting RPTP␤/ or attenuating Syndecan-3 signaling pathways may lead to more effective therapeutic strategies in treating prostate cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

Loss of Receptor Protein Tyrosine Phosphatase β/ζ (RPTPβ/ζ) Promotes Prostate Cancer Metastasis

Diamantopoulou

Kitsou

Ménashi

et al. 2012

Journal of Biological Chemistry

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“…Cell Proliferation Assay-To measure the number of cells, the 3-(4,5-dimethylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTT) assay was used as described previously (8). LNCaP cells were seeded at 5 ϫ 10 3 cells/well (or 20 ϫ 10 3 cells/well for the experiments using ODNs) in 24-well tissue culture plates in RPMI 1640 supplemented with 10% FBS.…”

Section: Methodsmentioning

confidence: 99%

“…Western Blot Analysis for HARP-The presence of HARP in the cell culture medium was investigated as described previously (8). The conditioned medium of the cells was incubated overnight with 100 l of heparin-Sepharose (Amersham Biosciences) at 4°C with continuous agitation.…”

Section: Methodsmentioning

confidence: 99%

“…Reverse transcriptase-PCRs were performed using the Access reverse transcriptase-PCR system (Promega) as described previously (8). Primers used for human HARP and ␤-actin were described previously (8).…”

Section: Methodsmentioning

confidence: 99%

“…A growing body of evidence indicates that HARP is involved in cell proliferation, migration, and differentiation and plays a significant role in several cellular processes (5,6). HARP seems to play a major role in physiological as well as tumor angiogenesis and is detected in various carcinomas, such as human breast and prostate cancer, neuroblastomas, gliomas, benign meningiomas, and small cell lung cancer and mammary tumors, exhibiting a proto-oncogene function (5)(6)(7)(8).…”

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Hydrogen Peroxide Stimulates Proliferation and Migration of Human Prostate Cancer Cells through Activation of Activator Protein-1 and Up-regulation of the Heparin Affin Regulatory Peptide Gene

Polytarchou

Hatziapostolou

Papadimitriou

2005

Journal of Biological Chemistry

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130

109

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It is becoming increasingly recognized that hydrogen peroxide (HP) plays a role in cell proliferation and migration. In the present study we found that exogenous HP significantly induced human prostate cancer LNCaP cell proliferation and migration. Heparin affin regulatory peptide (HARP) seems to be involved in the stimulatory effect of HP, because the latter had no effect on stably transfected LNCaP cells that did not express HARP. Moreover, HP significantly increased HARP mRNA and protein amounts in a concentration-and time-dependent manner. Curcumin and activator protein-1 (AP-1) decoy oligonucleotides abrogated both HPinduced HARP expression and LNCaP cell proliferation and migration. HP increased luciferase activity of the 5-flanking region of the HARP gene introduced in a reporter gene vector, an effect that was abolished when even one of the two putative AP-1 binding sites of the HARP promoter was mutated. The effect of HP seems to be due to the binding of Fra-1, JunD, and phospho-c-Jun to the HARP promoter. These results support the notion that HARP is important for human prostate cancer cell proliferation and migration, establish the role of AP-1 in the up-regulation of HARP expression by low concentrations of HP, and characterize the AP-1 dimers involved.A growing body of evidence correlates the production of reactive oxygen species with many aspects of cellular functions (1). Reactive oxygen species include the superoxide, hydrogen peroxide (HP), 2 and the hydroxyl radical. Of these, HP has the chemical stability required to establish significant steady-state concentrations in vivo (2, 3) and is small and uncharged, properties that allow it to freely diffuse across plasma membranes and make it an ideal candidate for a signaling molecule (4). Small quantities of HP are produced by all types of cells, and several signal transduction pathways in mammalian cells have been reported to be activated by HP, such as tyrosine kinases, mitogen-activated protein kinases, protein kinase C, the epidermal growth factor receptor, protein phosphatases, potassium channels, and the transcription factors activator protein-1 (AP-1), and nuclear factor B (reviewed in ref. 1).Heparin affin regulatory peptide (HARP), also called pleiotrophin or heparin-binding growth-associated molecule, is an 18-kDa secreted growth factor that displays high affinity for heparin. A growing body of evidence indicates that HARP is involved in cell proliferation, migration, and differentiation and plays a significant role in several cellular processes (5, 6). HARP seems to play a major role in physiological as well as tumor angiogenesis and is detected in various carcinomas, such as human breast and prostate cancer, neuroblastomas, gliomas, benign meningiomas, and small cell lung cancer and mammary tumors, exhibiting a proto-oncogene function (5-8).HARP is highly conserved among human, rat, bovine, and mouse species, and its gene is expressed in a highly restricted temporal and spatial pattern during development, suggesting that HARP may be an ...

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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

Polytarchou

Hatziapostolou

Poimenidi

et al. 2009

Intl Journal of Cancer

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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 b/f (RPTPb/f) 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 RPTPb/f is a mediator of the stimulatory effects of eNOS/NO on human endothelial and prostate cancer cell migration. '

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Heparin affin regulatory peptide is a key player in prostate cancer cell growth and angiogenicity

Abstract: HARP seems to act as an important regulator of diverse biological activities in human prostate cancer cells.

Cited by 40 publications

References 29 publications

Loss of Receptor Protein Tyrosine Phosphatase β/ζ (RPTPβ/ζ) Promotes Prostate Cancer Metastasis

Loss of Receptor Protein Tyrosine Phosphatase β/ζ (RPTPβ/ζ) Promotes Prostate Cancer Metastasis

Hydrogen Peroxide Stimulates Proliferation and Migration of Human Prostate Cancer Cells through Activation of Activator Protein-1 and Up-regulation of the Heparin Affin Regulatory Peptide Gene

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

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