Pleiotrophin expression correlates with melanocytic tumor progression and metastatic potential

Wu, Hong Gyun; Barusevicius, Alan; Babb, James S.; Klein‐Szanto, Andres J.; Godwin, Andrew K.; Elenitsas, Rosalie; Gelfand, Joel M.; Lessin, Stuart R.; Seykora, John T.

doi:10.1111/j.0303-6987.2005.00282.x

Cited by 54 publications

(35 citation statements)

References 25 publications

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“…Concomitantly, pleiotrophin is a proto-oncogene that functions as a mitogenic, anti-apoptotic, and tumor-transforming factor (4,(12)(13)(14)(15)(16)(17)(18). Furthermore, pleiotrophin stimulates epithelial-to-mesenchymal transition (EMT) (19), extensive remodeling of the malignant cell microenvironment (20), tumor angiogenesis (21,22), and metastasis (7).…”

Section: Pleiotrophin (Ptn)mentioning

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: Pleiotrophin (Ptn)mentioning

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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“…Pleiotrophin is expressed in different human cancers [3][4][5][6][7][8][9][10][11], and recently, PTN was identified in different subtypes of human breast cancers [12][13][14]. Targeting of constitutive PTN signaling in human breast cancers that inappropriately express Ptn by a dominant negative PTN reverses their malignant phenotype both in vitro and in vivo [15].…”

Section: Introductionmentioning

confidence: 99%

The receptor protein tyrosine phosphatase (RPTP)β/ζ is expressed in different subtypes of human breast cancer

Pérez-Piñera

García‐Suárez

Menéndez-Rodríguez

et al. 2007

Biochemical and Biophysical Research Communications

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Increasing evidence suggests mutations in human breast cancer cells that induce inappropriate expression of the 18kDa cytokine pleiotrophin (PTN, Ptn) initiate progression of breast cancers to a more malignant phenotype. Pleiotrophin signals through inactivating its receptor, the Receptor Protein Tyrosine Phosphatase (RPTP)β/ζ, leading to increased tyrosine phosphorylation of different substrate proteins of RPTPβ/ζ, including β-catenin, β-adducin, Fyn, GIT1/Cat-1, and P190RhoGAP. PTN signaling thus has wide impact on different important cellular systems. Recently, PTN was found to activate Anaplastic Lymphoma Kinase (ALK) through the PTN/RPTPβ/ζ signaling pathway; this discovery potentially is very important, since constitutive ALK activity of nucleophosmin (NPM)-ALK fusion protein is causative of anaplastic large cell lymphomas, and, activated ALK is found in other malignant cancers. Recently ALK was identified in each of 63 human breast cancers from 22 subjects. We now demonstrate that RPTPβ/ζ is expressed in each of these same 63 human breast cancers that previously were found to express ALK and in 10 additional samples of human breast cancer. RPTPβ/ζ furthermore was localized not only in its normal association with the cell membrane but also scattered in cytoplasm and in nuclei in different breast cancer cells and, in the case of infiltrating ductal carcinomas, the distribution of RPTPβ/ζ changes as the breast cancer become more malignant. The data suggest that the PTN/RPTPβ/ζ signaling pathway may be constitutively activated and potentially function to constitutively activate ALK in human breast cancer.

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“…Postnatally, PTN is down-regulated, and in most adult rodent and human tissues, it is present at very low levels. Its reactivation in adults strongly promotes angiogenesis and vascular growth in tumors (4, 8 -10), and it has served as a marker of cancer erosion, angiogenesis, and metastasis (11,12). In ectodermal derivatives, it promotes neurite outgrowth (13) and glial cell differentiation (5).…”

mentioning

confidence: 99%

The Pro-angiogenic Cytokine Pleiotrophin Potentiates Cardiomyocyte Apoptosis through Inhibition of Endogenous AKT/PKB Activity

Wei

Chesley

et al. 2007

Journal of Biological Chemistry

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Pleiotrophin is a development-regulated cytokine and growth factor that can promote angiogenesis, cell proliferation, or differentiation, and it has been reported to have neovasculogenic effects in damaged heart. Developmentally, it is prominently expressed in fetal and neonatal hearts, but it is minimally expressed in normal adult heart. Conversely, we show in a rat model of myocardial infarction and in human dilated cardiomyopathy that pleiotrophin is markedly up-regulated. To elucidate the effects of pleiotrophin on cardiac contractile cells, we employed primary cultures of rat neonatal and adult cardiomyocytes. We show that pleiotrophin is released from cardiomyocytes in vitro in response to hypoxia and that the addition of recombinant pleiotrophin promotes caspase-mediated genomic DNA fragmentation in a dose-and time-dependent manner. Functionally, it potentiates the apoptotic response of neonatal cardiomyocytes to hypoxic stress and to ultraviolet irradiation and of adult cardiomyocytes to hypoxia-reoxygenation. Moreover, UV-induced apoptosis in neonatal cardiomyocytes can be partially inhibited by small interfering RNA-mediated knockdown of endogenous pleiotrophin. Mechanistically, pleiotrophin antagonizes IGF-1 associated Ser-473 phosphorylation of AKT/PKB, and it concomitantly decreases both BAD and GSK3␤ phosphorylation. Adenoviral expression of constitutively active AKT and lithium chloride-mediated inhibition of GSK3␤ reduce the potentiated programmed cell death elicited by pleiotrophin. These latter data indicate that pleiotrophin potentiates cardiomyocyte cell death, at least partially, through inhibition of AKT signaling. In conclusion, we have uncovered a novel function for pleiotrophin on heart cells following injury. It fosters cardiomyocyte programmed cell death in response to pro-apoptotic stress, which may be critical to myocardial injury repair.

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Pleiotrophin expression correlates with melanocytic tumor progression and metastatic potential

Abstract: The results of this study confirm previous gene profiling data showing differential PTN expression between melanocytic nevi and melanomas. In addition, lesional PTN expression is associated with metastatic potential and may be a prognostic factor for melanomas.

Cited by 54 publications

References 25 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

The receptor protein tyrosine phosphatase (RPTP)β/ζ is expressed in different subtypes of human breast cancer

The Pro-angiogenic Cytokine Pleiotrophin Potentiates Cardiomyocyte Apoptosis through Inhibition of Endogenous AKT/PKB Activity

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