Abstract 4018: Crosstalk between the pleiotrophin-anaplastic lymphoma kinase axis and the protein tyrosine phosphatase ζ signaling pathways

Pleiotrophin (PTN) is a heparin-binding growth factor that can support tumor growth, invasion, angiogenesis, and metastasis. The mechanism of action (receptor signaling pathway) responsible for mediating PTN9s biological effects, however, is still controversial. Here we show that an antibody targeting the ligand-binding domain of anaplastic lymphoma kinase (ALK) is capable of blocking the signaling effects of PTN in a glioblastoma cell line that expresses high levels of ALK. This corroborates recent findings by Stylianou, et al. (2009), who showed disruption of PTN activity with a single chain variable IgG fragment that binds to the ALK ligand-binding domain. Furthermore, expression of protein tyrosine phosphatase receptor ζ (Ptprz) in cells resulted in crosstalk with the PTN-ALK signaling axis at the level of p38 MAPK. While PTN increased p38 MAPK phosphorylation, the presence of Ptprz decreased its phosphorylation, both at its basal as well as PTN-enhanced levels. Enhancement of p38 MAPK phosphorylation by PTN is possibly mediated through activation of MKK4, as it was phosphorylated in the presence of PTN. On the other hand, the mechanism for Ptprz-mediated suppression of p38 MAPK is not yet clear, as there was no change in phosphorylation of MKK3, MKK4, or MKK6 after its over-expression. These findings suggest that ALK is playing a direct role in PTN activity, and that the Ptprz signaling pathway may act in a separate but inter-connecting fashion. Parallel targeting of both the ALK and Ptprz signaling pathway may be necessary for the treatment of tumors (glioblastoma) expressing both membrane proteins. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4018.