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

  • Laboratory Investigation
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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.

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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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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.

Author information

Authors and Affiliations

  1. Neurosurgical Oncology Laboratory, Department of Neurosurgery, Brigham and Women’s Hospital & Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Mateo Ziu, Nils Ole Schmidt, Theresa G. Cargioli, Peter McL. Black & Rona S. Carroll

  2. Section of General Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    Mateo Ziu

  3. Hans-Dietrich Herrmann Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Nils Ole Schmidt

  4. Division of Hematology/Hematopoietic Cell Transplantation, and Neurosciences, City of Hope Cancer Center & Beckman Research Institute, Duarte, CA, USA

    Karen S. Aboody

  5. Department of Neurosurgery, Brigham and Women’s Hospital, 221 Longwood Avenue, LMRC Rm 121, Boston, MA, USA

    Rona S. Carroll

Authors
  1. Mateo Ziu
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  2. Nils Ole Schmidt
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  3. Theresa G. Cargioli
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  4. Karen S. Aboody
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  5. Peter McL. Black
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  6. Rona S. Carroll
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Corresponding author

Correspondence to Rona S. Carroll.

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† These authors contributed equally to this work.

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Ziu, M., Schmidt, N., Cargioli, T. et al. Glioma-produced extracellular matrix influences brain tumor tropism of human neural stem cells. J Neurooncol 79, 125–133 (2006). https://doi.org/10.1007/s11060-006-9121-5

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  • DOI: https://doi.org/10.1007/s11060-006-9121-5

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