Loss of receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ) promotes prostate cancer metastasis.
BACKGROUND
The role of pleiotrophin and its receptors RPTPβ/ζ and Syndecan-3 during tumor metastasis remains unknown.


RESULTS
RPTPβ/ζ knockdown initiates EMT, promotes pleiotrophin-mediated migration and attachment through Syndecan-3 and induces in vivo metastasis.


CONCLUSIONS
RPTPβ/ζ plays a suppressor-like role in prostate cancer metastasis.


CONCLUSIONS
Boosting RPTPβ/ζ or attenuating Syndecan-3 signaling pathways may lead to more effective therapeutic strategies in treating prostate cancer metastasis. Pleiotrophin is a growth factor that induces carcinogenesis. Despite the fact that many published reports focused on the role of pleiotrophin and its receptors, receptor protein tyrosine phosphatase (RPTPβ/ζ), and syndecan-3 during tumor development, no information is available regarding their function in tumor metastasis. To investigate the mechanism through which pleiotrophin regulates tumor metastasis, we used two different prostate carcinoma cell lines, DU145 and PC3, in which the expression of RPTPβ/ζ or syndecan-3 was down-regulated by the RNAi technology. The loss of RPTPβ/ζ expression initiated epithelial-to-mesenchymal transition (EMT) and increased the ability of the cells to migrate and invade. Importantly, the loss of RPTPβ/ζ expression increased metastasis in nude mice in an experimental metastasis assay. We also demonstrate that RPTPβ/ζ counterbalanced the pleiotrophin-mediated syndecan-3 pathway. While the inhibition of syndecan-3 expression inhibited the pleiotrophin-mediated cell migration and attachment through the Src and Fak pathway, the inhibition of RPTPβ/ζ expression increased pleiotrophin-mediated migration and attachment through an interaction with Src and the subsequent activation of a signal transduction pathway involving Fak, Pten, and Erk1/2. Taken together, these results suggest that the loss of RPTPβ/ζ may contribute to the metastasis of prostate cancer cells by inducing EMT and promoting pleiotrophin activity through the syndecan-3 pathway.
Division of Genetics, Cell, and Developmental Biology, Department of Biology, University of Patras, 26500 Patras, Greece.
Zoi
Z
Diamantopoulou
Paraskevi
P
Kitsou
Suzanne
S
Menashi
Jose
J
Courty
Panagiotis
P
Katsoris
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D053670:Syndecan-3 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D053670:Syndecan-3; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5