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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)26953-26964
Number of pages12
JournalJournal of Biological Chemistry
Volume280
Issue number29
DOIs
Publication statusPublished - Jul 22 2005

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Glioblastoma
Microarrays
Tumors
Brain
Growth
Protein Tyrosine Phosphatases
Cell Surface Receptors
Cell culture
Purification
Intercellular Signaling Peptides and Proteins
Cells
Tissue
Amino Acids
Messenger RNA
Tissue Array Analysis
Processing
anaplastic lymphoma kinase
pleiotrophin
Proteins
Brain Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lu, K. V., Jong, K. A., Kim, G. Y., Singh, J., Dia, E. Q., Yoshimoto, K., ... Mischel, P. S. (2005). Differential induction of glioblastoma migration and growth by two forms of pleiotrophin. Journal of Biological Chemistry, 280(29), 26953-26964. https://doi.org/10.1074/jbc.M502614200

Differential induction of glioblastoma migration and growth by two forms of pleiotrophin. / Lu, Kan V.; Jong, Kimberly A.; Kim, Gloria Y.; Singh, Jatinder; Dia, Ederlyn Q.; Yoshimoto, Koji; Wang, Maria Y.; Cloughesy, Timothy F.; Nelson, Stanley F.; Mischel, Paul S.

In: Journal of Biological Chemistry, Vol. 280, No. 29, 22.07.2005, p. 26953-26964.

Research output: Contribution to journalArticle

Lu, KV, Jong, KA, Kim, GY, Singh, J, Dia, EQ, Yoshimoto, K, Wang, MY, Cloughesy, TF, Nelson, SF & Mischel, PS 2005, 'Differential induction of glioblastoma migration and growth by two forms of pleiotrophin', Journal of Biological Chemistry, vol. 280, no. 29, pp. 26953-26964. https://doi.org/10.1074/jbc.M502614200
Lu, Kan V. ; Jong, Kimberly A. ; Kim, Gloria Y. ; Singh, Jatinder ; Dia, Ederlyn Q. ; Yoshimoto, Koji ; Wang, Maria Y. ; Cloughesy, Timothy F. ; Nelson, Stanley F. ; Mischel, Paul S. / Differential induction of glioblastoma migration and growth by two forms of pleiotrophin. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 29. pp. 26953-26964.
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