Differential induction of glioblastoma migration and growth by two forms of pleiotrophin

Kan V. Lu, Kimberly A. Jong, Gloria Y. Kim, Jatinder Singh, Ederlyn Q. Dia, Koji Yoshimoto, Maria Y. Wang, Timothy F. Cloughesy, Stanley F. Nelson, Paul S. Mischel

研究成果: Contribution to journalArticle査読

101 被引用数 (Scopus)

抄録

Glioblastoma is the most common malignant brain tumor of adults and one of the most lethal cancers. The secreted growth factor pleiotrophin (PTN) promotes glioblastoma migration and proliferation, initiating its oncogenic activities through two cell surface receptors, the protein tyrosine phosphatase receptor ζ (PTPRZ1) and the anaplastic lymphoma kinase (ALK), respectively. Here, we report on the presence and purification of two naturally occurring forms of PTN (18 and 15 kDa) that differentially promote glioblastoma migration and proliferation. Using a panel of glioblastoma cell lines, including low passage patient-derived cultures, we demonstrate that PTN15 promotes glioblastoma proliferation in an ALK-dependent fashion, whereas immobilized PTN18 promotes haptotactic migration of glioblastoma cells in a PTPRZ1-dependent fashion. Mass spectrometric analysis indicated that PTN15 differs from PTN18 by processing of 12 C-terminal amino acids. To demonstrate clinical relevance, we show that PTN15, PTN18, and PTPRZ1 are significantly overexpressed in glioblastoma relative to normal brain at both mRNA and protein levels using microarray, Western blot, and tissue microarray analyses on human tumors. These results indicate that the PTN18-PTPRZ1 and the PTN15-ALK signaling pathways represent potentially important therapeutic targets for glioblastoma invasion and growth.

本文言語英語
ページ(範囲)26953-26964
ページ数12
ジャーナルJournal of Biological Chemistry
280
29
DOI
出版ステータス出版済み - 7 22 2005
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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