Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3

Johnson, Mahlon D.; O’Connell, Mary J.; Facik, Michael S.; Maurer, Paul K.; Jahromi, Babak S.; Pilcher, Webster H.

doi:10.1007/s11060-011-0736-9

Cited by 13 publications

(15 citation statements)

References 38 publications

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“…These findings are consistent with the known effects of STAT3 activation on cell proliferation, apoptosis and angiogenesis (20,(23)(24)(25). In a previous study, we demonstrated that cerebrospinal fluid stimulated the phosphorylation/activation of STAT3 in grade I/II primary meningioma cell cultures (6). Furthermore, our previous study revealed that the mitogenic effects of cerebrospinal fluid on WHO grade I and II meningioma cells appear to be exerted, in part, via the activation of STAT3 (6).…”

Section: Discussionsupporting

confidence: 89%

“…In a previous study, we demonstrated that cerebrospinal fluid stimulated the phosphorylation/activation of STAT3 in grade I/II primary meningioma cell cultures (6). Furthermore, our previous study revealed that the mitogenic effects of cerebrospinal fluid on WHO grade I and II meningioma cells appear to be exerted, in part, via the activation of STAT3 (6). In addition, we have identified activation of STAT3 in grade I and II meningiomas, with increased phosphorylation/activation in grade II tumors (9).…”

Section: Discussionmentioning

confidence: 87%

“…Nonetheless, in our previous studies, cerebrospinal fluid, which activates STAT3 and stimulates meningioma cell proliferation, promoted STAT3 phosphorylation that could be detected in meningioma cells at 72 h following treatment suggesting phospho-STAT3 maintenance or stability in at least some in vitro conditions. Furthermore, extensive phosphorylation of p44/42 MAPK and Akt was detected in frozen tissue (1,3,6). Thus, in cases of extensive cellular activation, phospho-STAT3 may be stable and reliably detected in tissue frozen relatively promptly following surgical extirpation.…”

Section: Discussionmentioning

confidence: 95%

“…Previous studies by our group and others have identified several key signaling pathways that are activated in meningiomas, including the mitogen-activated protein kinase (MAPK) kinase kinase-MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK1)-p44/42 MAPK cascade and the phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB/Akt)-mammalian target of rapamycin (mTOR) and JAK1-STAT3 pathways, which regulate the proliferation of meningiomas (1,2,(3)(4)(5) and appear to be activated, in part, by components of the cerebrospinal fluid (6) and/or paracrine effects that activate receptor/kinases, such as the epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) receptor/kinases, in meningiomas (6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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STAT3 activation and risk of recurrence in meningiomas

2017

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Abstract. Several studies have suggested that activation of signal transducer and activator of transcription 3 (STAT3) is associated with initiation, progression and metastasis of numerous types of malignancy. However, the role of the Janus kinase-interleukin 6-STAT3 signaling pathway in the pathogenesis and recurrence of meningiomas is unknown. The present study evaluated STAT3 activation by western blotting and immunohistochemistry and assessed its association with Ki-67 labeling in 13 cases of meningioma in which frozen tissue and ≥5.5-year follow-up information were available, and in formalin-fixed meningioma tissues from 14 cases with an 8.4-year follow-up. The results of the western blot analysis indicated that STAT3 phosphorylation was markedly higher in grade II meningiomas compared with that in grade I, with mean densitometric values of 8.6 and 1.7 following normalization to actin, respectively. High STAT3 phosphorylation/activation was identified in 2 of 3 recurrent World Health Organization (WHO) grade I meningiomas and 0 of 3 non-recurrent meningiomas. Strong STAT3 phosphorylation/activation signal was also found in 2 of 4 recurrent grade II meningiomas and 1 of 3 non-recurrent cases. According to the immunohistochemistry results, phospho-STAT3 was not increased in WHO grade II tumors compared with that in grade I tumors, and was not significantly different between recurrent and non-recurrent cases. Ki-67 labeling was significantly increased in grade II vs. grade I tumors, and was also significantly increased in recurrent compared with non-recurrent grade I meningiomas. The results of the current study suggest that, while detection of phosphorylated/activated STAT3 may be useful in isolated cases, identifying activation may be of little value in predicting recurrence.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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STAT3 activation and risk of recurrence in meningiomas

2017

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“…Human cerebrospinal fluid from patients without neurological disease. As meningiomas are bathed in cerebrospinal fluid, which has been demonstrated to affect meningioma cell proliferation (13), its effects on APOBEC3B were evaluated in the current study. Remnant, discarded lumbar cerebrospinal fluid was collected at the University of Rochester Medical Center and sent to the Department of Pathology between March 2009 and September 2012.…”

Section: Introductionmentioning

confidence: 99%

APOBEC3B expression in human leptomeninges and meningiomas

2016

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Abstract. Nucleic acid-editing enzymes of the apolipoprotein B mRNA-editing enzyme (APOBEC) family have been associated with somatic mutation in cancer. However, the role of APOBEC catalytic subunit 3B (APOBEC3B) editing in the pathogenesis of base substitutions in meningiomas is unknown. In the present study, the expression of APOBEC3B was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses in five fetal and one adult human leptomeninges and 38 meningiomas. Genomic DNA was sequenced using the Illumina Tru-Seq Cancer Panel. Three meningioma primary cultures were also established and treated with cerebrospinal fluid form patients without neurological disease or platelet-derived growth factor-BB (PDGF-BB), prior to evaluation of APOBEC3B expression. By western blotting, APOBEC3B was revealed to be present in 100% of the fetal leptomeninges, and in 88% of World Health Organization grade I, 100% of grade II and 83% of grade III meningiomas tested, but was not different between grades. RT-qPCR revealed no difference in the mRNA expression of APOBEC3B between grades. Sequencing revealed no elevated levels of the C>T mutations that are characteristic of APOBEC3B editing of genomic DNA. Treatment with cerebrospinal fluid and PDGF-BB had no effect on APOBEC3B protein expression in the leptomeningeal or meningioma cells. These findings suggest that the mutations associated with increased APOBEC3B expression may not be central to the pathogenesis of meningiomas. IntroductionRecent studies have indicated that normal cellular enzymatic activity may contribute to the genomic changes associated with various neoplasias (1-3). Apolipoprotein B mRNA-editing enzymes (APOBEC) comprise a family of enzymes that protect immune function and are involved in mRNA editing; their cytosine deaminase activity may also induce base substitutions in the genomes of malignancies (1,2).APOBEC3B is a cytosine deaminase that is responsible for the deamination of cytosines in the genome of host cells, producing cytosine to thymidine mutations (2). Recently studies have found that APOBEC3B is overexpressed in several types of malignancy, resulting in clusters of C>T mutations that are considered to be the signature of APOBEC mutation in tumors. Analysis of whole-genome and whole-exome sequencing data from various types of malignancy have implicated APOBEC members in mRNA editing and the production of cytosine mutation clusters in the development or progression of numerous neoplastic processes, encompassing lung, breast, hepatic and hematopoietic malignancies (4-9). APOBEC3B overexpression has been identified in breast, head and neck cancers (7-10). Although APOBEC3B expression has not been studied in meningiomas, the presence of C>T point mutations in some meningioma cases raises the possibility that APOBEC3B may participate in the pathogenesis of at least a subset of meningiomas (11).The present study evaluated APOBEC3B expression in addition to mutations in a series of normal leptomeninges, an...

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ADAM12 Silencing Mediated by FOXC2 Represses Meningioma Progression Through Inactivating the JAK1/STAT3/VEGFA Pathway

Zhang,

Yang

2024

Biochem Genet

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Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3

Cited by 13 publications

References 38 publications

STAT3 activation and risk of recurrence in meningiomas

STAT3 activation and risk of recurrence in meningiomas

APOBEC3B expression in human leptomeninges and meningiomas

ADAM12 Silencing Mediated by FOXC2 Represses Meningioma Progression Through Inactivating the JAK1/STAT3/VEGFA Pathway

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