Tumor necrosis-initiated complement activation stimulates proliferation of medulloblastoma cells

Adrian J. Maurer, Phillip A. Bonney, Lucas C. Toho, Chad A. Glenn, Shweta Agarwal, James D. Battiste, Kar Ming Fung, Michael E. Sughrue

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective and design: We sought to determine the effect of necrosis-induced activation of the complement protein C3 in medulloblastoma.Materials/methods: Twelve medulloblastoma surgical specimens were evaluated for complement activation using immunohistochemistry, with H&E stains performed on adjacent tissue sections to determine the relationship of complement activation to necrotic tissue. Flow cytometry and Western blot were performed on three established medulloblastoma lines and one surgically-procured cell culture to determine expression of C3a receptor (C3aR) in medulloblastoma. In vitro proliferation of siRNA C3aR knockdown cells was compared to that of control siRNA cells with cell line Daoy.Results: Three surgical specimens were found to have necrosis on H&E sections. In each case, iC3b staining was identified on adjacent sections, limited to the necrotic region. In no case did necrosis occur without iC3b staining on adjacent sections. C3aR protein was demonstrated on both the three established cell lines and on the surgical culture. Proliferation assays of Daoy cells with siRNA knockdown vs. control siRNA revealed significantly reduced proliferation at 72 h (p = 0.001).Conclusions: Necrosis is associated with complement activation in medulloblastoma. Medulloblastoma cells express C3aR, and siRNA-mediated knockdown of C3aR inhibits proliferation of these cells in vitro.

Original languageEnglish (US)
Pages (from-to)185-192
Number of pages8
JournalInflammation Research
Volume64
Issue number3-4
DOIs
StatePublished - Mar 13 2015

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Medulloblastoma
Complement Activation
Necrosis
Small Interfering RNA
Cell Proliferation
Complement C3b
Neoplasms
Staining and Labeling
Cell Line
Complement C3
Flow Cytometry
Complement System Proteins
Coloring Agents
Cell Culture Techniques
Western Blotting
Immunohistochemistry
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology

Cite this

Maurer, A. J., Bonney, P. A., Toho, L. C., Glenn, C. A., Agarwal, S., Battiste, J. D., ... Sughrue, M. E. (2015). Tumor necrosis-initiated complement activation stimulates proliferation of medulloblastoma cells. Inflammation Research, 64(3-4), 185-192. https://doi.org/10.1007/s00011-015-0796-y

Tumor necrosis-initiated complement activation stimulates proliferation of medulloblastoma cells. / Maurer, Adrian J.; Bonney, Phillip A.; Toho, Lucas C.; Glenn, Chad A.; Agarwal, Shweta; Battiste, James D.; Fung, Kar Ming; Sughrue, Michael E.

In: Inflammation Research, Vol. 64, No. 3-4, 13.03.2015, p. 185-192.

Research output: Contribution to journalArticle

Maurer, AJ, Bonney, PA, Toho, LC, Glenn, CA, Agarwal, S, Battiste, JD, Fung, KM & Sughrue, ME 2015, 'Tumor necrosis-initiated complement activation stimulates proliferation of medulloblastoma cells', Inflammation Research, vol. 64, no. 3-4, pp. 185-192. https://doi.org/10.1007/s00011-015-0796-y
Maurer, Adrian J. ; Bonney, Phillip A. ; Toho, Lucas C. ; Glenn, Chad A. ; Agarwal, Shweta ; Battiste, James D. ; Fung, Kar Ming ; Sughrue, Michael E. / Tumor necrosis-initiated complement activation stimulates proliferation of medulloblastoma cells. In: Inflammation Research. 2015 ; Vol. 64, No. 3-4. pp. 185-192.
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