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Conserved Molecular Underpinnings and Characterization of a Role for Caveolin-1 in the Tumor Microenvironment of Mature T-Cell Lymphomas.

Herek TA, Shew TD, Spurgin HN, Cutucache CE - PLoS ONE (2015)

Bottom Line: Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics.From these results, we sought to characterize a role for caveolin-1 (CAV1), a gene with previous description in the progression of both solid and hematological tumors.Taken together, these results demonstrate a role for CAV1 in the tumor microenvironment of mature T-cell malignancies and point toward potential prognostic implications.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Nebraska at Omaha, Omaha, Nebraska, United States of America.

ABSTRACT
Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics. Much work has been done to gain greater insights into distinguishing features among malignant subtypes, but there also exists a need to identify unifying characteristics to assist in rapid diagnosis and subsequent potential treatment. Herein, we investigated gene expression data of five different mature T-cell lymphoma subtypes (n = 187) and found 21 genes to be up- and down-regulated across all malignancies in comparison to healthy CD4(+) and CD8(+) T-cell controls (n = 52). From these results, we sought to characterize a role for caveolin-1 (CAV1), a gene with previous description in the progression of both solid and hematological tumors. Caveolin-1 was upregulated, albeit with a heterogeneous nature, across all mature T-cell lymphoma subtypes, a finding confirmed using immunohistochemical staining on an independent sampling of mature T-cell lymphoma biopsies (n = 65 cases). Further, stratifying malignant samples in accordance with high and low CAV1 expression revealed that higher expression of CAV1 in mature T-cell lymphomas is analogous with an enhanced inflammatory and invasive gene expression profile. Taken together, these results demonstrate a role for CAV1 in the tumor microenvironment of mature T-cell malignancies and point toward potential prognostic implications.

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Long non-Coding RNA 273 is computationally predicted to interact with members of a CAV1-interaction network.(A) Boxplot of normalized AFFX-HUMRGE/M10098_5_at (LINC00273) probe signal for CAV1-Low and CAV1-High expression groups. Continuous line represents median value, discontinuous line represents mean value. (B) CAV1-interacting proteins upregulated in the CAV1-High expression group. Interaction network viewed in String evidence view, connection lines are defined by in-Fig box. (C) CAV1-interacting proteins upregulated in the CAV1-Low expression group. Interaction network viewed in String evidence view, connection lines are defined by in-Fig box.
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pone.0142682.g004: Long non-Coding RNA 273 is computationally predicted to interact with members of a CAV1-interaction network.(A) Boxplot of normalized AFFX-HUMRGE/M10098_5_at (LINC00273) probe signal for CAV1-Low and CAV1-High expression groups. Continuous line represents median value, discontinuous line represents mean value. (B) CAV1-interacting proteins upregulated in the CAV1-High expression group. Interaction network viewed in String evidence view, connection lines are defined by in-Fig box. (C) CAV1-interacting proteins upregulated in the CAV1-Low expression group. Interaction network viewed in String evidence view, connection lines are defined by in-Fig box.

Mentions: Strikingly, an uncharacterized long, intergenic non-coding RNA (LINC00273) was found to be expressed 3-fold higher in CAV1-Low T-cell lymphoma samples compared to CAV1-High (Fig 4A). As long non-coding RNAs have been implicated in RNA-protein binding complexes, we sought to investigate if LINC00273 represented a potential RNA-protein interaction (RPI) partner with CAV1 and CAV1-interacting proteins, as CAV1 expression was the basis upon which the abovementioned groups were stratified. Using STRING v10, we determined the predicted CAV1-interactions networks for genes upregulated in both CAV1-High (Fig 4B) and CAV1-Low groups (Fig 4C). Of the 1,758 genes upregulated in CAV1-High samples, 38 proteins were modeled to interact (either direct, or indirect) with CAV1 (Fig 4B). The CAV1-High interaction network featured 100 protein-protein interactions, of which the protein constituents were found to be enriched in GO biological processes for regulation of cell differentiation (p = 2.7x10−4), cell migration (p = 4.2x10−4), cell proliferation (p = 7.2x10−4), apoptotic processes (p = 2.87x10−4), and the KEGG TGF-beta signaling pathway (p = 1.9x10−6). Conversely, only 4 proteins of the 866 genes upregulated in CAV1-Low samples were modeled to interact with CAV1 (Fig 4C). This protein network featured 4 protein-protein interactions and was found to be enriched for the GO biological processes of fibroblast growth factor receptor signaling (p = 1.91x10−4) and ERBB signaling (p = 5.46x10−4).


Conserved Molecular Underpinnings and Characterization of a Role for Caveolin-1 in the Tumor Microenvironment of Mature T-Cell Lymphomas.

Herek TA, Shew TD, Spurgin HN, Cutucache CE - PLoS ONE (2015)

Long non-Coding RNA 273 is computationally predicted to interact with members of a CAV1-interaction network.(A) Boxplot of normalized AFFX-HUMRGE/M10098_5_at (LINC00273) probe signal for CAV1-Low and CAV1-High expression groups. Continuous line represents median value, discontinuous line represents mean value. (B) CAV1-interacting proteins upregulated in the CAV1-High expression group. Interaction network viewed in String evidence view, connection lines are defined by in-Fig box. (C) CAV1-interacting proteins upregulated in the CAV1-Low expression group. Interaction network viewed in String evidence view, connection lines are defined by in-Fig box.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643970&req=5

pone.0142682.g004: Long non-Coding RNA 273 is computationally predicted to interact with members of a CAV1-interaction network.(A) Boxplot of normalized AFFX-HUMRGE/M10098_5_at (LINC00273) probe signal for CAV1-Low and CAV1-High expression groups. Continuous line represents median value, discontinuous line represents mean value. (B) CAV1-interacting proteins upregulated in the CAV1-High expression group. Interaction network viewed in String evidence view, connection lines are defined by in-Fig box. (C) CAV1-interacting proteins upregulated in the CAV1-Low expression group. Interaction network viewed in String evidence view, connection lines are defined by in-Fig box.
Mentions: Strikingly, an uncharacterized long, intergenic non-coding RNA (LINC00273) was found to be expressed 3-fold higher in CAV1-Low T-cell lymphoma samples compared to CAV1-High (Fig 4A). As long non-coding RNAs have been implicated in RNA-protein binding complexes, we sought to investigate if LINC00273 represented a potential RNA-protein interaction (RPI) partner with CAV1 and CAV1-interacting proteins, as CAV1 expression was the basis upon which the abovementioned groups were stratified. Using STRING v10, we determined the predicted CAV1-interactions networks for genes upregulated in both CAV1-High (Fig 4B) and CAV1-Low groups (Fig 4C). Of the 1,758 genes upregulated in CAV1-High samples, 38 proteins were modeled to interact (either direct, or indirect) with CAV1 (Fig 4B). The CAV1-High interaction network featured 100 protein-protein interactions, of which the protein constituents were found to be enriched in GO biological processes for regulation of cell differentiation (p = 2.7x10−4), cell migration (p = 4.2x10−4), cell proliferation (p = 7.2x10−4), apoptotic processes (p = 2.87x10−4), and the KEGG TGF-beta signaling pathway (p = 1.9x10−6). Conversely, only 4 proteins of the 866 genes upregulated in CAV1-Low samples were modeled to interact with CAV1 (Fig 4C). This protein network featured 4 protein-protein interactions and was found to be enriched for the GO biological processes of fibroblast growth factor receptor signaling (p = 1.91x10−4) and ERBB signaling (p = 5.46x10−4).

Bottom Line: Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics.From these results, we sought to characterize a role for caveolin-1 (CAV1), a gene with previous description in the progression of both solid and hematological tumors.Taken together, these results demonstrate a role for CAV1 in the tumor microenvironment of mature T-cell malignancies and point toward potential prognostic implications.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Nebraska at Omaha, Omaha, Nebraska, United States of America.

ABSTRACT
Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics. Much work has been done to gain greater insights into distinguishing features among malignant subtypes, but there also exists a need to identify unifying characteristics to assist in rapid diagnosis and subsequent potential treatment. Herein, we investigated gene expression data of five different mature T-cell lymphoma subtypes (n = 187) and found 21 genes to be up- and down-regulated across all malignancies in comparison to healthy CD4(+) and CD8(+) T-cell controls (n = 52). From these results, we sought to characterize a role for caveolin-1 (CAV1), a gene with previous description in the progression of both solid and hematological tumors. Caveolin-1 was upregulated, albeit with a heterogeneous nature, across all mature T-cell lymphoma subtypes, a finding confirmed using immunohistochemical staining on an independent sampling of mature T-cell lymphoma biopsies (n = 65 cases). Further, stratifying malignant samples in accordance with high and low CAV1 expression revealed that higher expression of CAV1 in mature T-cell lymphomas is analogous with an enhanced inflammatory and invasive gene expression profile. Taken together, these results demonstrate a role for CAV1 in the tumor microenvironment of mature T-cell malignancies and point toward potential prognostic implications.

Show MeSH
Related in: MedlinePlus