Journal of Neuro-Oncology

, Volume 79, Issue 2, pp 125–133 | Cite as

Glioma-produced extracellular matrix influences brain tumor tropism of human neural stem cells

  • Mateo Ziu
  • Nils Ole Schmidt
  • Theresa G. Cargioli
  • Karen S. Aboody
  • Peter McL. Black
  • Rona S. Carroll
Laboratory Investigation
First Online:
Received:
Accepted:

Summary

A major obstacle in the treatment of gliomas is the invasive capacity of the tumor cells. Previous studies have demonstrated the capability of neural stem cells (NSCs) to target these disseminated tumor cells and to serve as therapeutic delivery vehicles. Less is known about the factors involved in brain tumor tropism of NSCs and their interactions within the tumor environment. As gliomas progress and invade, an extensive modulation of the extracellular matrix (ECM) occurs. Tumor-ECM derived from six glioblastoma cell lines, ECM produced by normal human astrocytes and purified ECM compounds known to be upregulated in the glioma environment were analyzed for their effects on NSCs motility in vitro. We found that tumor-produced ECM was highly permissive for NSC migration. Laminin was the most permissive substrate for human NSC migration, and tenascin-C the strongest inducer of a directed human NSC migration (haptotaxis). A positive correlation between the degree of adhesion and migration of NSCs on different ECM compounds exists, as for glioma cells. Our in vitro data suggest that the ECM of malignant gliomas is a modulator of NSC migration. ECM proteins preferentially expressed in areas of glioma cell invasion may provide a permissive environment for NSC tropism to disseminated tumor cells.

Keywords

brain tumor extracellular matrix migration stem cells therapeutics 

Abbreviations

Astro-ECM

Astrocyte-derived ECM

ECM

Extracellular matrix

G-ECM

Glioma-derived ECM

HB1.F3 h-NSCs

HB1.F3 human neural stem cells

NSC

Neural stem cell

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Notes

Acknowledgements

This work was supported by National Institute of Health, Layton Biosciences Inc., Boston Neurosurgical Foundation, and by a fellowship grant of the German Research Foundation (DFG: to N.O.S.).

We are grateful to Wendy Yang and Svenja Zapf for their technical support. We further thank Dr Seung Kim for his critical suggestions in preparing the manuscript.

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Mateo Ziu
    • 1
    • 2
  • Nils Ole Schmidt
    • 1
    • 3
  • Theresa G. Cargioli
    • 1
  • Karen S. Aboody
    • 4
  • Peter McL. Black
    • 1
  • Rona S. Carroll
    • 1
    • 5
  1. 1.Neurosurgical Oncology LaboratoryDepartment of Neurosurgery, Brigham and Women’s Hospital & Children’s Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Section of General SurgeryVanderbilt University Medical CenterNashvilleUSA
  3. 3.Hans-Dietrich Herrmann Laboratory for Brain Tumor BiologyDepartment of Neurosurgery, University Hospital Hamburg-EppendorfHamburgGermany
  4. 4.Division of Hematology/Hematopoietic Cell Transplantation, and NeurosciencesCity of Hope Cancer Center & Beckman Research InstituteDuarteUSA
  5. 5.Department of NeurosurgeryBrigham and Women’s HospitalBostonUSA

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