Editors' ChoiceCancer

New connections: Pleiotrophin and glioma

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Sci. Signal.  05 Sep 2017:
Vol. 10, Issue 495, eaap8372
DOI: 10.1126/scisignal.aap8372

The cytokine pleiotrophin promotes the invasion and vascularization of glioma.

Understanding the signaling pathways that trigger the initiation and promote the progression of glioma may yield new therapeutic strategies for improving the prognosis of this cancer. Two papers suggest that targeting the cytokine pleiotrophin may suppress different processes that contribute to the lethality of glioma. Using a mouse model that recapitulated the invasion pattern of a particular glioma subtype and coculture systems, Qin et al. (see also Guttman) found that pleiotrophin in complex with three binding partners (SPARC, SPARCL1, and HSP90B) was secreted from neural precursor cells and enhanced the invasion of glioma cells toward the subventricular zone. The effect of pleiotrophin on invasion was partially mediated by the receptor PTPRZ and involved the activation of the Rho-ROCK pathway in glioma cells. In the second paper, Zhang et al. focused on the effect of pleiotrophin on endothelial cells in angiogenesis, a process by which new blood vessels are formed and which enables glioma growth. Glioma cells that released pleiotrophin formed larger tumors with more blood vessels and increased concentrations of VEGF (another proangiogenic factor) near the blood vessels. Mice had smaller gliomas and survived longer when treated with inhibitors of ALK (another receptor for pleiotrophin) or an inhibitor of the VEGF receptor (VEGFR). Thus, pleiotrophin released by neural precursor cells promotes glioma invasion in part through PTPRZ, whereas pleiotrophin released from glioma cells acts in an autocrine manner to enhance angiogenesis through ALK and indirectly through VEGFR.

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