IGF-1 receptor inhibition by picropodophyllin in medulloblastoma

Sachiko Ohshima-Hosoyama, Tohru Hosoyama, Laura D. Nelon, Charles Keller

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The insulin-like growth factor-1 receptor (Igf1r) is a multifunctional membrane-associated tyrosine kinase associated with regulation of transformation, proliferation, differentiation and apoptosis. Increased IGF pathway activity has been reported in human and murine medulloblastoma. Tumors from our genetically-engineered medulloblastoma mouse model over-express Igf1r, and thus this mouse model is a good platform with which to study the role of Igf1r in tumor progression. We hypothesize that inhibition of IGF pathway in medulloblastoma can slow or inhibit tumor growth and metastasis. To test our hypothesis, we tested the role of IGF in tumor growth in vitro by treatment with the tyrosine kinase small molecule inhibitor, picropodophyllin (PPP), which strongly inhibits the IGF pathway. Our results demonstrate that PPP-mediated downregulation of the IGF pathway inhibits mouse tumor cell growth and induces apoptotic cell death in vitro in primary medulloblastoma cultures that are most reflective of tumor cell behavior in vivo.

Original languageEnglish (US)
Pages (from-to)727-732
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume399
Issue number4
DOIs
StatePublished - Sep 2010
Externally publishedYes

Fingerprint

IGF Type 1 Receptor
Medulloblastoma
Tumors
Somatomedin Receptors
Somatomedins
Neoplasms
Protein-Tyrosine Kinases
Growth
Cell growth
Cell death
Cell culture
Inhibition (Psychology)
picropodophyllin
Cell Death
Down-Regulation
Cells
Apoptosis
Neoplasm Metastasis
Membranes
Molecules

Keywords

  • Apoptosis
  • Insulin-like growth factor-1 receptor
  • Medulloblastoma
  • Picropodophyllin
  • Tumor growth

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

IGF-1 receptor inhibition by picropodophyllin in medulloblastoma. / Ohshima-Hosoyama, Sachiko; Hosoyama, Tohru; Nelon, Laura D.; Keller, Charles.

In: Biochemical and Biophysical Research Communications, Vol. 399, No. 4, 09.2010, p. 727-732.

Research output: Contribution to journalArticle

Ohshima-Hosoyama, Sachiko ; Hosoyama, Tohru ; Nelon, Laura D. ; Keller, Charles. / IGF-1 receptor inhibition by picropodophyllin in medulloblastoma. In: Biochemical and Biophysical Research Communications. 2010 ; Vol. 399, No. 4. pp. 727-732.
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