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Schwann cell-conditioned medium inhibits angiogenesis.
D Huang1, J L Rutkowski, G M Brodeur
1Department of Pediatrics, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA.
Cancer Research
|November 21, 2000
Summary
Schwann cells in neuroblastoma tumors may inhibit blood vessel growth by producing tissue inhibitor of metalloproteinase-2 (TIMP-2). This may explain why stroma-rich neuroblastomas have better prognoses.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Neuroblastomas are heterogeneous tumors with neuroblastic/ganglionic and Schwann cells.
- Tumor prognosis correlates with Schwannian stroma content; stroma-rich tumors have favorable outcomes.
- Previous research linked high vascularity to aggressive neuroblastoma, while stroma-rich tumors showed low vascularity.
Purpose of the Study:
- To investigate if Schwann cells inhibit angiogenesis in neuroblastoma.
- To assess the effect of conditioned medium from Schwann cells on endothelial cell proliferation and migration.
- To examine in vivo and in vitro angiogenesis using conditioned medium from normal and tumor-derived Schwann cells.
Main Methods:
- Conditioned medium from normal human Schwann cells and tumor-derived Schwann cells was used.
- Endothelial cell proliferation and migration assays were performed.
- In vivo and in vitro angiogenesis assays were conducted.
- Expression studies, including immunohistochemistry, identified specific molecules.
Main Results:
- Schwann cells, from both normal nerve and tumor tissue, produce potent angiogenesis inhibitors.
- Tissue inhibitor of metalloproteinase-2 (TIMP-2) was detected in conditioned medium and within Schwann cells and ganglion cells in tumors.
- Tumors with abundant Schwannian stroma exhibited low vascularity.
Conclusions:
- Schwann cells likely inhibit angiogenesis in neuroblastoma.
- The production of TIMP-2 by Schwann cells may contribute to the low vascularity and favorable prognosis of stroma-rich neuroblastomas.
- Schwann cells play a significant role in regulating tumor microenvironment and behavior.