Expression of platelet-derived growth factors, transforming growth factors, and the ros gene in a variety of primary human brain tumors

Mapstone, Timothy B.; McMichael, Margaret; Goldthwait, David A.

doi:10.1097/00006123-199102000-00007

Cited by 31 publications

(13 citation statements)

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“…Increased cytokine gene expression or cytokine production has been detected in brain tissue and in cerebrospinal fluid after certain infections and brain diseases (8,37,38). TGF-,B has been found in glioblastoma patients (39,40) and in the brain tissues of AIDS patients (41,42). It is possible that the local production of cytokines plays a pivotal role in CNS inflammation and altered neuronal function via a paracrine or an autocrine mechanism.…”

Section: Discussionmentioning

confidence: 99%

Effects of transforming growth factor-beta on murine astrocyte glutamine synthetase activity. Implications in neuronal injury.

Chao¹,

Hu²,

Tsang³

et al. 1992

J. Clin. Invest.

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Cytokines have been implicated in the pathogenesis of a number of brain diseases in which neurological dysfunction has been attributed to a change in amino acid neurotransmitter metabolism. In the present in vitro study, we investigated the effects ofcytokines on astrocyte glutamine synthetase (GS) activity and subsequently on N-methyl-D-asparate (NMDA) receptor-mediated neurotoxicity. Proinflammatory cytokines IL-la, IL-1,6, and IL-6 at a concentration of 20 ng/ml did not affect GS activity; however, tumor necrosis factor-a inhibited this activity by 20% in mixed neuronal/astrocyte cultures. Treatment for 24 h with transforming growth factor (TGF)-f91 or -,62 inhibited up to 60% GS activity. TGF-#2 also inhibited GS in enriched astrocyte cultures with an ED5o of 10 pg/ml. Antibodies specific to TGF-,62 blocked this effect. Treatment of astrocytes with TGF-jf2 (250 pg/ml) resulted in markedly dilated rough endoplasmic reticulum. Since astrocyte GS may play a protective role in NMDA receptor-mediated neurotoxicity, we treated mixed neuronal/astrocyte cultures with TGF-,2 (250 pg/ml) and found a threefold potentiation of NMDA receptor-mediated neurotoxicity. These data suggest that 8 impairs astrocyte GS function and enhances neurotoxicity, thus providing insight into understanding one mechanism of cytokine-mediated central nervous system disease. (J. Clin. Invest.

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Section: Discussionmentioning

confidence: 99%

Effects of transforming growth factor-beta on murine astrocyte glutamine synthetase activity. Implications in neuronal injury.

Chao¹,

Hu²,

Tsang³

et al. 1992

J. Clin. Invest.

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“…The c-ROS receptor has been reported to be ectopically expressed in 30% of human glioma cell lines and tumors, suggesting ROS may contribute to glioma initiation and/or maintenance (5)(6)(7)(8)(9)(10). However, the consequences of ectopic ROS expression on tumorigenesis have never been addressed experimentally.…”

Section: Introductionmentioning

confidence: 99%

ROS Fusion Tyrosine Kinase Activates a SH2 Domain–Containing Phosphatase-2/Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Signaling Axis to Form Glioblastoma in Mice

et al. 2006

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Glioblastoma multiforme is the most common and lethal form of primary brain cancer. Diagnosis of this advanced glioma has a poor prognosis due to the ineffectiveness of current therapies. Aberrant expression of receptor tyrosine kinases (RTK) in glioblastoma multiformes is suggestive of their role in initiation and maintenance of these tumors of the central nervous system. In fact, ectopic expression of the orphan RTK ROS is a frequent event in human brain cancers, yet the pathologic significance of this expression remains undetermined. Here, we show that a glioblastoma-associated, ligand-independent rearrangement product of ROS (FIG-ROS) cooperates with loss of the tumor suppressor gene locus Ink4a;Arf to produce glioblastomas in the mouse. We show that this FIG-ROS-mediated tumor formation in vivo parallels the activation of the tyrosine phosphatase SH2 domaincontaining phosphatase-2 (SHP-2) and a phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling axis in tumors and tumor-derived cell lines. We have established a fully penetrant preclinical model for adult onset of glioblastoma multiforme in keeping with major genetic events observed in the human disease. These findings provide novel and important insights into the role of ROS and SHP-2 function in solid tumor biology and set the stage for preclinical testing of targeted therapeutic approaches. (Cancer Res 2006; 66(15): 7473-81)

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“…In addition, ROS1 expression has been shown to be associated with the differentiation of tumors, including gastric adenocarcinomas (11), astrocytomas (26), and invasive breast carcinomas (25). Further studies are required in order to address the function of ROS1 signaling in the context of cell differentiation and transformation.…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic c-ros oncogene 1 receptor tyrosine kinase expression may be associated with the development of human oral squamous cell carcinoma

et al. 2015

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Abstract. The c-ros oncogene 1 receptor tyrosine kinase (ROS1) gene encodes a proto-oncogenic protein that has been demonstrated to be involved in the pathogenesis of several types of cancer. The present study aimed to analyze the expression of ROS1 in human oral squamous cell carcinomas (OSCCs), and investigate the association between its expression and the clinicopathological parameters of patients with OSCC. Paraffin-embedded OSCC tissues from 31 patients were obtained and the expression of ROS1 was analyzed by immunohistochemistry. The cellular location of ROS1 was determined by immunofluorescence in human oral cancer CAL-27 cells. The association of clinicopathological characteristics and survival rates with ROS1 expression were assessed. The results revealed that ROS1 was exclusively localized in the cytoplasm of the OSCC tissues (24/30, 80.0%), and in the cytoplasm of adjacent dysplastic epithelial tissues (2/15, 13.3%) (P<0.001). The moderate to strong expression of ROS1 in the cytoplasm was higher in OSCC tissues than in the normal epithelial tissues adjacent to the tumor (67.7 vs. 0%, P=0.001). The results of the Kaplan-Meier analysis and multivariate Cox regression analysis indicated that there was no association between the 5-year survival rate of patients and the cytoplasmic (P=0.28 and P=0.60, respectively) or nuclear expression (P=0.90 and P=0.31, respectively) of ROS1. These results suggest that the cytoplasmic expression level of ROS1 may be associated with the development of OSCC.

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Expression of platelet-derived growth factors, transforming growth factors, and the ros gene in a variety of primary human brain tumors

Cited by 31 publications

References 0 publications

Effects of transforming growth factor-beta on murine astrocyte glutamine synthetase activity. Implications in neuronal injury.

Effects of transforming growth factor-beta on murine astrocyte glutamine synthetase activity. Implications in neuronal injury.

ROS Fusion Tyrosine Kinase Activates a SH2 Domain–Containing Phosphatase-2/Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Signaling Axis to Form Glioblastoma in Mice

Cytoplasmic c-ros oncogene 1 receptor tyrosine kinase expression may be associated with the development of human oral squamous cell carcinoma

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