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Brain Tumor Pathology

, Volume 28, Issue 1, pp 33–42 | Cite as

Persistent roles of signal transduction of platelet-derived growth factor B in genesis, growth, and anaplastic transformation of gliomas in an in-vivo serial transplantation model

  • Rina Torisu
  • Satoshi O. SuzukiEmail author
  • Kenta Masui
  • Koji Yoshimoto
  • Masahiro Mizoguchi
  • Makoto Hashizume
  • Peter Canoll
  • James E. Goldman
  • Tomio Sasaki
  • Toru Iwaki
Original Article

Abstract

We previously reported that retrovirally transduced platelet-derived growth factor-B (PDGFB) in glial progenitors of the rat cerebral white matter, subventricular zone, or brain stem induced malignant brain tumors closely resembling human glioblastoma (GBM). While human GBMs may progress over the period of several months to a few years, prospective, long-term in-vivo observation of histological changes of the tumor tissues is not feasible in these models, because the animals undergo rapid tumor progression and mortality within approximately 1 month. We thus performed successive, long-term in-vivo transplantation of the PDGFB-induced tumor cells into the rat cerebrum. Primary retroviral transduction of PDGFB in the glial progenitors of the rat basal ganglia induced malignant glioma resembling human GBM or anaplastic oligodendroglioma (AOL) consisting of relatively monomorphous tumor cells expressing markers for the oligodendrocyte lineage. In the course of long-term successive transplantation, tumor cells presented pleomorphism as well as focal GFAP expression. This suggests that secondary chromosomal aberration and dysregulation of gene expression following accelerated cell cycle by PDGFB stimulation would induce morphological and immunophenotypic changes in tumor cells. Furthermore, while the primary tumors contained only a minor fraction of proviral GFP-expressing or hemagglutinin-expressing cells, most tumor cells came to express these proviral genes in the course of serial transplantation suggesting a persistent role of PDGFB-expressing cells in maintenance and growth of the tumors. This model would be useful for investigation of the long-term effects of PDGFB stimulation in glioma tissues on anaplastic evolution.

Keywords

Oligodendrocyte precursors PDGF Glioma Animal model Successive transplantation 

Notes

Acknowledgments

The authors would like to thank Dr Kensuke Sasaki for instruction in statistical analysis, Dr Yoshihiro Seki for helpful comments and supports, and Ms Sachiko Nagae and Kimiko Sato for their excellent technical instruction and assistance (all from Department of Neuropathology, Kyushu University). They also thank Dr Hideki Horikawa (Department of Neuropsychiatry, Kyushu University) for instruction of ELISA, and Dr Sumako Nishimura and Dr Takeshi Yasunaga (Hitachi Medical Corporation) for their excellent technical assistance with open-MRI.

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Copyright information

© The Japan Society of Brain Tumor Pathology 2010

Authors and Affiliations

  • Rina Torisu
    • 1
    • 2
  • Satoshi O. Suzuki
    • 1
    Email author
  • Kenta Masui
    • 1
  • Koji Yoshimoto
    • 2
  • Masahiro Mizoguchi
    • 2
  • Makoto Hashizume
    • 3
  • Peter Canoll
    • 4
  • James E. Goldman
    • 4
  • Tomio Sasaki
    • 2
  • Toru Iwaki
    • 1
  1. 1.Department of Neuropathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Neurosurgery, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of Advanced Medical Initiatives, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  4. 4.Department of PathologyColumbia University College of Physicians and SurgeonsNew YorkUSA

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