A rat glioma model, CNS-1, with invasive characteristics similar to those of human gliomas: A comparison to 9L gliosarcoma

Kruse, Carol A.; Molleston, Michael C.; Parks, Elizabeth Prout; Schiltz, Patric M.; Kleinschmidt‐DeMasters, Bette K.; Hickey, William F.

doi:10.1007/bf01052919

Cited by 91 publications

(66 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous work from our laboratories has shown that the rat gliosarcoma cell line 9L, characterized in vivo as a poorly invasive brain tumor [40], does not express B/b endogenously [33] and, when transfected with the full-length protein, is also unable to cleave it at the ADAMTS site [34]. Moreover, both control and B/b-overexpressing 9L cells exhibit the same non-infiltrative behavior when grown as intracranial grafts and produce tumors that do not differ in size [34].…”

Section: Discussionmentioning

confidence: 99%

“…The rat CNS-1 glioma cell line was grown at 5% CO 2 in RPMI-1640 medium supplemented with 10% fetal calf serum, 100 U/ml penicillin, and 100 μg/ml streptomycin (Invitrogen, Carlsbad CA) [40]. These cells express and cleave B/b when grown as intracranial grafts but have no production of B/b in culture, likely due to the absence of CNS-specific inducing factors [33].…”

Section: Cells and Antibodiesmentioning

confidence: 99%

See 1 more Smart Citation

BEHAB/brevican requires ADAMTS-mediated proteolytic cleavage to promote glioma invasion

2008

View full text Add to dashboard Cite

Malignant gliomas are the most common and deadly primary brain tumors, due to their infiltrative invasion of the normal neural tissue that makes them virtually impossible to completely eliminate. We have previously identified and characterized the proteoglycan BEHAB/brevican in gliomas and have demonstrated that upregulation and cleavage of this CNS-specific molecule promote glioma invasion. Here, we have further investigated if the proteolytic processing of BEHAB/ brevican by metalloproteases of the ADAMTS family is a necessary step in mediating its proinvasive effect in glioma. By generating a site-specific ( 396 SRG 398 → NVY) mutant form resistant to ADAMTS cleavage, we have shown that the predominant proteolytic processing of BEHAB/ brevican by glioma cells occurs only at this site. More importantly, "uncleavable" BEHAB/ brevican is unable to enhance glioma cell invasion in vitro and tumor progression in vivo. In addition, our results suggest that the full-length protein and its cleavage products may act independently because the mutant form does not exert a dominant negative effect on normal BEHAB/brevican expression or cleavage. These results illustrate how the regulated processing of major components of the neural extracellular matrix has important functional implications in glioma progression. In addition, our findings underscore the relevance of the ADAMTS family of metalloproteases as attractive targets for novel pharmacological approaches in glioma therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Cells and Antibodiesmentioning

confidence: 99%

BEHAB/brevican requires ADAMTS-mediated proteolytic cleavage to promote glioma invasion

2008

View full text Add to dashboard Cite

show abstract

“…2A). CNS-1 cells have been shown to express GFAP, S100, and importantly, CPEB1 (3,18). Indeed, when we quantified Western blot analyses of astrocyte cultures and compared them with CNS1 cultures, the MTDH/AEG-1 level is significantly higher in CNS1 cells.…”

Section: Cpeb1 Regulates Mtdh/aeg-1 Expressionmentioning

confidence: 99%

CPEB1 Regulates the Expression of MTDH/AEG-1 and Glioblastoma Cell Migration

Kochanek

Wells

2013

Molecular Cancer Research

View full text Add to dashboard Cite

Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is an mRNA-binding protein present in both neurons and glia. CPEB1 is capable of both repressing mRNA translation and activating it depending upon its phosphorylation state. CPEB1-bound mRNAs are held in translational dormancy until CPEB1 is phosphorylated, leading to the cytoplasmic polyadenylation of the bound mRNA that triggers translation. Here, we show that CPEB1 can bind to and regulate translation of the mRNA-encoding metadherin (MTDH, also known as AEG-1 and Lyric) in the rat glioblastoma cell line CNS1. MTDH/AEG-1 is being revealed as a critical signaling molecule in tumor progression, playing roles in invasion, metastasis, and chemoresistance. By using a mutant of CPEB1 that cannot be phosphorylated (thereby holding target mRNAs in translational arrest), we show that inhibiting CPEB1-mediated translation blocks MTDH/AEG-1 expression in vitro and inhibits glioblastomas tumor growth in vivo. CPEB1-mediated translation is likely to impact several signaling pathways that may promote tumor progression, but we present evidence suggesting a role in directed cell migration in glioblastoma cells. In addition, reporter mRNA containing CPEB1-binding sites is transported to the leading edge of migrating cells and translated, whereas the same mRNA with point mutations in the binding sites is synthesized perinuclearly. Our findings show that CPEB1 is hyperactive in rat glioblastoma cells and is regulating an important cohort of mRNAs whose increased translation is fueling the progression of tumor proliferation and dispersal in the brain. Thus, targeting CPEB1-mediated mRNA translation might be a sound therapeutic approach. Mol Cancer Res; 11(2); 149-60. Ó2012 AACR.

show abstract

“…in Lewis rats as previously described (29). Approximately 10 6 cells were implanted aseptically, as with the 9L/LacZ, 2-3 weeks before the study.…”

Section: Animals and Tumor Modelsmentioning

confidence: 99%

Changes in oxygenation of intracranial tumors with carbogen: A BOLD MRI and EPR oximetry study

Dunn

O’Hara

Wadghiri

et al. 2002

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Purpose: To examine, using blood oxygen level dependent (BOLD) MRI and EPR oximetry, the changes in oxygenation of intracranial tumors induced by carbogen breathing. Materials and Methods:The 9L and CNS-1 intracranial rat tumor models were imaged at 7T, before and during carbogen breathing, using a multi-echo gradient-echo (GE) sequence to map R 2 *. On a different group of 9L tumors, tissue pO 2 was measured using EPR oximetry with lithium phthalocyanine as the oxygen-sensitive material. Results:The average decline in R 2 * with carbogen breathing was 13 Ϯ 1 s -1 in the CNS-1 tumors and 29 Ϯ 4 s -1 in the 9L tumor. The SI vs. TE decay curves indicate the presence of multiple components in the tumor. Tissue pO 2 in the two 9L tumors measured was 8.6 Ϯ 0.5 and 3.6 Ϯ 0.6 mmHg during air breathing, and rose to 20 Ϯ 7 and 16 Ϯ 4 mmHg (mean Ϯ SE) with carbogen breathing. Significant changes were observed by 10 minutes, but changes in pO 2 and R 2 * continued in some subjects over the entire 40 minutes. Conclusion:EPR results indicate that glial sarcomas may be radiobiologically hypoxic. Both EPR and BOLD data indicate that carbogen breathing increases brain tumor oxygenation. These data support the use of BOLD imaging to monitor changes in oxygenation in brain tumors.

show abstract

A rat glioma model, CNS-1, with invasive characteristics similar to those of human gliomas: A comparison to 9L gliosarcoma

Cited by 91 publications

References 12 publications

BEHAB/brevican requires ADAMTS-mediated proteolytic cleavage to promote glioma invasion

BEHAB/brevican requires ADAMTS-mediated proteolytic cleavage to promote glioma invasion

CPEB1 Regulates the Expression of MTDH/AEG-1 and Glioblastoma Cell Migration

Changes in oxygenation of intracranial tumors with carbogen: A BOLD MRI and EPR oximetry study

Contact Info

Product

Resources

About