Skip to main content

Advertisement

SpringerLink
Log in

Growth properties of SF188/V+ human glioma in rats in vivo observed by magnetic resonance imaging

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

SF188/V+ is a highly vascular human glioma model that is based on transfection of vascular endothelial growth factor (VEGF) cDNA into SF188/V− cells. This study aims to assess its growth and vascularity properties in vivo in a rat model. Thirty-two adult rats were inoculated with SF188/V+ tumor cells, and, for comparison, five were inoculated with SF188/V− tumor cells. Several conventional magnetic resonance imaging (MRI) sequences were acquired, and several quantitative structural (T2 and T1), functional [isotropic apparent diffusion coefficient (ADC) and blood flow], and molecular [protein and peptide-based amide proton transfer (APT)] MRI parameters were mapped on a 4.7 T animal scanner. In rats inoculated with SF188/V+ tumor cells, conventional T2-weighted images showed a highly heterogeneous tumor mass, and post-contrast T1-weighted images showed a heterogeneous, strong enhancement of the mass. There were moderate increases in T2, T1, and ADC, and large increases in blood flow and APT in the tumor, compared to contralateral brain tissue. Microscopic examination revealed prominent vascularity and hemorrhage in the VEGF-secreting xenografts as compared to controls, and immunohistochemical staining confirmed increased expression of VEGF in tumor xenografts. Our results indicate that the SF188/V+ glioma model exhibits some MRI and histopathology features that closely resemble human glioblastoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507

    Article  PubMed  CAS  Google Scholar 

  2. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  PubMed  CAS  Google Scholar 

  3. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 15:459–466

    Article  Google Scholar 

  4. McGirt MJ, Than KD, Weingart JD, Chaichana KL, Attenello FJ, Olivi A, Laterra J, Kleinberg LR, Grossman SA, Brem H, Quinones-Hinojosa A (2009) Gliadel (BCNU) wafer plus concomitant temozolomide therapy after primary resection of glioblastoma multiforme. J Neurosurg 110:583–588

    Article  PubMed  CAS  Google Scholar 

  5. Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845

    Article  PubMed  CAS  Google Scholar 

  6. Jain RK, Duda DG, Clark JW, Loeffler JS (2006) Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol 3:24–40

    Article  PubMed  CAS  Google Scholar 

  7. Barth RF (1998) Rat brain tumor models in experimental neuro-oncology: the 9L, C6, T9, F98, RG2 (D74), RT-2 and CNS-1 gliomas. J Neuro-Oncol 36:91–102

    Article  CAS  Google Scholar 

  8. Barth RF, Kaur B (2009) Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas. J Neuro-Oncol 94:299–312

    Article  Google Scholar 

  9. Goldbrunner RH, Wagner S, Roosen K, Tonn JC (2000) Model for assessment of angiogenesis in gliomas. J Neuro-Oncol 50:53–62

    Article  CAS  Google Scholar 

  10. Candolfi M, Curtin JF, Nichols WS, Muhammad AG, King GD, Pluhar GE, McNiel EA, Ohlfest JR, Freese AB, Moore PF, Lerner J, Lowenstein PR, Castro MG (2007) Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression. J Neuro-Oncol 85:133–148

    Article  Google Scholar 

  11. Ma J, Zhou-Li F, Klein-Szanto A, Gallo JM (1998) Modulation of angiogenesis by human glioma xenograft models that differentially express vascular endothelial growth factor. Clin Exp Metastasis 16:559–568

    Article  PubMed  CAS  Google Scholar 

  12. Zhou Q, Guo P, Wang X, Nuthalapati S, Gallo JM (2007) Preclinical pharmacokinetic and pharmacodynamic evaluation of metronomic and conventional temozolomide dosing regimens. J Pharmacol Exp Ther 321:265–275

    Article  PubMed  CAS  Google Scholar 

  13. Zhou Q, Guo P, Gallo JM (2008) Impact of angiogenesis inhibition by sunitinib on tumor distribution of temozolomide. Clin Cancer Res 14:1540–1549

    Article  PubMed  Google Scholar 

  14. Verma R, Zacharaki EI, Ou Y, Cai H, Chawla S, Lee SK, Melhem ER, Wolf R, Davatzikos C (2008) Multiparametric tissue characterization of brain neoplasms and their recurrence using pattern classification of MR images. Acad Radiol 15:966–977

    Article  PubMed  Google Scholar 

  15. Chang SM, Nelson S, Vandenberg S, Cha S, Prados M, Butowski N, McDermott M, Parsa AT, Aghi M, Clarke J, Berger M (2009) Integration of preoperative anatomic and metabolic physiologic imaging of newly diagnosed glioma. J Neuro-Oncol 92:401–415

    Article  Google Scholar 

  16. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, DeGroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972

    Article  PubMed  Google Scholar 

  17. Chenevert TL, McKeever PE, Ross BD (1997) Monitoring early response of experimental brain tumors to therapy using diffusion magnetic resonance imaging. Clin Cancer Res 3:1457–1466

    PubMed  CAS  Google Scholar 

  18. Chenevert TL, Stegman LD, Taylor JMG, Roberson PL, Greenberg HS, Rehemtulla A, Ross BD (2000) Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. J Nat Cancer Inst 92:2029–2035

    Article  PubMed  CAS  Google Scholar 

  19. Sinha S, Bastin ME, Whittle IR, Wardlaw JM (2002) Diffusion tensor MR imaging of high-grade cerebral gliomas. Am J Neuroradiol 23:520–527

    PubMed  Google Scholar 

  20. Lu S, Ahn D, Johnson G, Cha S (2003) Peritumoral diffusion tensor imaging of high-grade gliomas and metastatic brain tumors. Am J Neuroradiol 24:937–941

    PubMed  Google Scholar 

  21. Wolf RL, Wang JJ, Wang SM, Melhem ER, O’Rourke DM, Judy KD, Detre JA (2005) Grading of CNS neoplasms using continuous arterial spin labeled perfusion MR imaging at 3 tesla. J Magn Reson Imaging 22:475–482

    Article  PubMed  Google Scholar 

  22. Barrett T, Brechbiel M, Bernardo M, Choyke PL (2007) MRI of tumor angiogenesis. J Magn Reson Imaging 26:235–249

    Article  PubMed  Google Scholar 

  23. Alger JR, Frank JA, Bizzi A, Fulham MJ, Desouza BX, BDuhaney MO, Inscoe SW, Blake JL, van Zijl PCM, Moonen CTW, Dickiro G (1990) Metabolism of human gliomas—assessment with H-1 MR spectroscopy and F-18 fluorodeoxyglucose PET. Radiology 177:633–641

    PubMed  CAS  Google Scholar 

  24. Nelson SJ, Graves E, Pirzkall A, Li X, Chan AA, Vigneron DB, McKnight TR (2002) In vivo molecular imaging for planning radiation therapy of gliomas: an application of 1H MRSI. J Magn Reson Imaging 16:464–476

    Article  PubMed  Google Scholar 

  25. Ward KM, Aletras AH, Balaban RS (2000) A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). J Magn Reson 143:79–87

    Article  PubMed  CAS  Google Scholar 

  26. Zhou J, Payen J, Wilson DA, Traystman RJ, van Zijl PCM (2003) Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med 9:1085–1090

    Article  PubMed  CAS  Google Scholar 

  27. Zhou J, Lal B, Wilson DA, Laterra J, van Zijl PCM (2003) Amide proton transfer (APT) contrast for imaging of brain tumors. Magn Reson Med 50:1120–1126

    Article  PubMed  Google Scholar 

  28. Zhou J, Tryggestad E, Wen Z, Lal B, Zhou T, Grossman R, Wang S, Yan K, Fu D-X, Ford E, Tyler B, Blakeley J, Laterra J, van Zijl PCM (2011) Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nat Med 17:130–134

    Article  PubMed  CAS  Google Scholar 

  29. Wen Z, Hu S, Huang F, Wang X, Guo L, Quan X, Wang S, Zhou J (2010) MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast. NeuroImage 51:616–622

    Article  PubMed  Google Scholar 

  30. Jia GA, Abaza R, Williams JD, Zynger DL, Zhou JY, Shah ZK, Patel M, Sammet S, Wei L, Bahnson RR, Knopp MV (2011) Amide proton transfer MR imaging of prostate cancer: a preliminary study. J Magn Reson Imaging 33:647–654

    Article  PubMed  Google Scholar 

  31. Williams DS, Detre JA, Leigh JS, Koretsky AP (1992) Magnetic resonance imaging of perfusion using spin inversion of arterial water. Proc Natl Acad Sci USA 89:212–216

    Article  PubMed  CAS  Google Scholar 

  32. Gomori JM, Grossman RI, Goldberg HI, Zimmerman RA, Bilaniuk LT (1985) Intracranial hematomas—imaging by high-field MR. Radiology 157:87–93

    PubMed  CAS  Google Scholar 

  33. Silva AC, Kim S-G, Garwood M (2000) Imaging blood flow in brain tumors using arterial spin labeling. Magn Reson Med 44:169–173

    Article  PubMed  CAS  Google Scholar 

  34. Bernsen HJJA, van der Koger AJ (1999) Antiangiogenic therapy in brain tumor models. J Neuro-Oncol 45:247–255

    Article  CAS  Google Scholar 

  35. Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, Loeffler JS, Batchelor TT, Sorensen AG (2009) Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 6:327–338

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. James M. Gallo (Temple University, Philadelphia, PA, USA; currently Mount Sinai School of Medicine, New York, NY, USA) for providing the glioma xenograft cell lines used in this study. The parental SF188/V− cell line was originally provided by the Brain Tumor Research Center, University of California, San Francisco, CA, USA. Dr. Jianguo Ma and Dr. James M. Gallo, et al. (Temple University, Philadelphia, PA, USA) made the SF188/V+ cell model. This study was supported in part by Grants from NIH (EB009112, EB009731, EB015032, and EB015555), by the American Physicians Fellowship (APF) for Medicine in Israel (Grossman), and by the Research Scholar Grants, #116293-RSG-08-119-01-CCE from the American Cancer Society (Tyler).

Disclosure

The authors have no conflicting interests.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Rachel Grossman, Betty Tyler & Henry Brem

  2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Charles G. Eberhart

  3. Division of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Park 336, Baltimore, MD, 21287, USA

    Silun Wang, Zhibo Wen & Jinyuan Zhou

  4. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    De-Xue Fu

  5. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA

    Jinyuan Zhou

Authors
  1. Rachel Grossman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Betty Tyler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Henry Brem
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Charles G. Eberhart
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Silun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. De-Xue Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhibo Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jinyuan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jinyuan Zhou.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 119 kb)

Supplementary material 2 (PDF 299 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grossman, R., Tyler, B., Brem, H. et al. Growth properties of SF188/V+ human glioma in rats in vivo observed by magnetic resonance imaging. J Neurooncol 110, 315–323 (2012). https://doi.org/10.1007/s11060-012-0974-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-012-0974-5

Keywords

Search

Navigation