Society of University SurgeonsContinuous local delivery of interferon-β stabilizes tumor vasculature in an orthotopic glioblastoma xenograft resection model
Section snippets
Cell lines
Three grade IV glioblastoma cell lines with infiltrative patterns of growth were engineered to express the firefly luciferase gene: GBM6-luc (provided by Dr. D. James, San Francisco, CA), MT330-luc (provided by Dr. C. Duntsch, Memphis, TN), and SJG2-luc (provided by C. Morton, Memphis, TN). These 3 cell lines were used for all in vitro and in vivo experiments. Hs294T (American Type Culture Collection, Manassas, VA) a melanoma cell was used as a positive control for in vitro studies.
In vitro hIFN-β sensitivity studies
GBM6-luc and
Glioblastomas are minimally sensitive to rhIFN-β in vitro
We sought to assess the direct effect of rhIFN-β on glioblastoma viability in vitro. GBM6-luc, MT330-luc, and SJG2-luc cells were plated at an appropriate density in 96-well plates and allowed to adhere overnight. The next day, the cells were exposed to increasing doses of rhIFN-β from 0 to 10,000 U/mL. After 96 hours, the AlamarBlue assay was used to quantify the number of viable cells. All 3 cell lines were found to be only slightly sensitive to hIFN-β; GBM6, MT330, and SJG2 were respectively
Discussion
Glioblastomas are aggressive, highly vascular neoplasms with a dismal prognosis that produce excessive amounts of multiple angiogenic factors, such as basic fibroblast growth factor, vascular endothelial growth factor, and angiopoietins.4, 5, 6, 7 Our laboratory has demonstrated previously that systemic hIFN-β delivered through a gene therapy approach stabilizes the vasculature of subcutaneous (heterotopic) glioblastoma xenografts by increasing the number of pericytes.13 We sought to assess the
References (25)
- et al.
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
(2009) - et al.
Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers
Semin Radiat Oncol
(1996) - et al.
Improved intratumoral oxygenation through vascular normalization increases glioma sensitivity to ionizing radiation
Int J Radiat Oncol Biol Phys
(2010) - et al.
Interferon beta-mediated vessel stabilization improves delivery and efficacy of systemically administered topotecan in a murine neuroblastoma model
J Pediatr Surg
(2007) - et al.
Purification of recombinant adeno-associated virus type 8 vectors by ion exchange chromatography generates clinical grade vector stock
J Virol Methods
(2004) - et al.
In vivo bioluminescence imaging for early detection and monitoring of disease progression in a murine model of neuroblastoma
J Pediatr Surg
(2007) - et al.
Enforced expression of tissue inhibitor of matrix metalloproteinase-3 affects functional capillary morphogenesis and inhibits tumor growth in a murine tumor model
Blood
(2002) - et al.
Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer
Am J Pathol
(2001) - et al.
Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma
N Engl J Med
(2005) - et al.
Angiogenesis in gliomas: biology and molecular pathophysiology
Brain Pathol
(2005)
Angiopoietin-4 promotes glioblastoma progression by enhancing tumor cell viability and angiogenesis
Cancer Res
Expression and hypoxic regulation of angiopoietins in human astrocytomas
Neuro Oncol
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2016, Biochemical and Biophysical Research CommunicationsCitation Excerpt :All quantitative data represent at least three independent experiments performed in duplicate, at least, and presented as mean ± S.D. Data were analyzed by two-tailed Student's t-test, and considered significant at p values < 0.05. We previously found that SJG2 and MT330 GBM cells were relatively insensitive to the antiproliferative effect of IFN [22]. We first tested the activity of bortezomib alone on GBM cell viability by exposing SJG2 and MT330 cells to varying concentrations of bortezomib (from 0 to 20 nM) for 72 h. Bortezomib resulted in a dose-dependent inhibition of cell proliferation with the greatest effect obtained at highest concentration (20 nM) in SJG2 and MT330 (Fig. 1A) cells, but cells showed a slight sensitivity at low concentrations (<5 nM).
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Supported by the Assisi Foundation of Memphis, the US Public Health Service Childhood Solid Tumor Program Project Grant No. CA23099, the Cancer Center Support Grant No. 21766 from the National Cancer Institute, Grant No. CA133322 from the National Cancer Institute, and by the American Lebanese Syrian Associated Charities (ALSAC).