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FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma

FilGAP, a Rho GTPase-activating protein (GAP), acts as a mediator of Rho/ROCK (Rho-associated protein kinase)-dependent amoeboid movement, and its knockdown results in Rac-driven mesenchymal morphology. Herein, we focus on the possible roles of FilGAP expression in normal and malignant lymphocytes....

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Autores principales: Nishi, Tatsuya, Takahashi, Hiroyuki, Hashimura, Miki, Yoshida, Tsutomu, Ohta, Yasutaka, Saegusa, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472203/
https://www.ncbi.nlm.nih.gov/pubmed/25641953
http://dx.doi.org/10.1002/cam4.423
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author Nishi, Tatsuya
Takahashi, Hiroyuki
Hashimura, Miki
Yoshida, Tsutomu
Ohta, Yasutaka
Saegusa, Makoto
author_facet Nishi, Tatsuya
Takahashi, Hiroyuki
Hashimura, Miki
Yoshida, Tsutomu
Ohta, Yasutaka
Saegusa, Makoto
author_sort Nishi, Tatsuya
collection PubMed
description FilGAP, a Rho GTPase-activating protein (GAP), acts as a mediator of Rho/ROCK (Rho-associated protein kinase)-dependent amoeboid movement, and its knockdown results in Rac-driven mesenchymal morphology. Herein, we focus on the possible roles of FilGAP expression in normal and malignant lymphocytes. Eighty-three cases of follicular lymphoma (FL), 84 of diffuse large B-cell lymphoma (DLBCL), and 25 of peripheral T-cell lymphoma (PTCL), as well as 10 of normal lymph nodes, were immunohistochemically investigated. In normal lymph nodes, FilGAP immunoreactivity was significantly higher in lymphocytes in the mantle zone as compared to those in the germinal center and paracortical areas. In contrast, the expression levels of both cytoplasmic and perinuclear Rac1 were significantly lower in the germinal center as compared to paracortical regions, suggesting that changes in the FilGAP/Rac axis may occur in B-cell lineages. In malignant lymphomas, FilGAP expression was significantly higher in B-cell lymphomas than PTCL, and the immunohistochemical scores were positively correlated with cytoplasmic Rac1 scores in FL and DLBCL, but not in PTCL. Patients with FL and germinal center B-cell-like (GCB)-type DLBCL showing high FilGAP scores had poor overall survival rates as compared to the low-score patients. Moreover, multivariate Cox regression analysis showed that a high FilGAP score was a significant and independent unfavorable prognostic factor in FL, but not in DLBCL. In conclusion, FilGAP may contribute to change in cell motility of B-lymphocytes. In addition, its expression appears to be useful for predicting the behavior of B-cell lymphoma, in particular FL.
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spelling pubmed-44722032015-06-23 FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma Nishi, Tatsuya Takahashi, Hiroyuki Hashimura, Miki Yoshida, Tsutomu Ohta, Yasutaka Saegusa, Makoto Cancer Med Cancer Research FilGAP, a Rho GTPase-activating protein (GAP), acts as a mediator of Rho/ROCK (Rho-associated protein kinase)-dependent amoeboid movement, and its knockdown results in Rac-driven mesenchymal morphology. Herein, we focus on the possible roles of FilGAP expression in normal and malignant lymphocytes. Eighty-three cases of follicular lymphoma (FL), 84 of diffuse large B-cell lymphoma (DLBCL), and 25 of peripheral T-cell lymphoma (PTCL), as well as 10 of normal lymph nodes, were immunohistochemically investigated. In normal lymph nodes, FilGAP immunoreactivity was significantly higher in lymphocytes in the mantle zone as compared to those in the germinal center and paracortical areas. In contrast, the expression levels of both cytoplasmic and perinuclear Rac1 were significantly lower in the germinal center as compared to paracortical regions, suggesting that changes in the FilGAP/Rac axis may occur in B-cell lineages. In malignant lymphomas, FilGAP expression was significantly higher in B-cell lymphomas than PTCL, and the immunohistochemical scores were positively correlated with cytoplasmic Rac1 scores in FL and DLBCL, but not in PTCL. Patients with FL and germinal center B-cell-like (GCB)-type DLBCL showing high FilGAP scores had poor overall survival rates as compared to the low-score patients. Moreover, multivariate Cox regression analysis showed that a high FilGAP score was a significant and independent unfavorable prognostic factor in FL, but not in DLBCL. In conclusion, FilGAP may contribute to change in cell motility of B-lymphocytes. In addition, its expression appears to be useful for predicting the behavior of B-cell lymphoma, in particular FL. BlackWell Publishing Ltd 2015-06 2015-01-29 /pmc/articles/PMC4472203/ /pubmed/25641953 http://dx.doi.org/10.1002/cam4.423 Text en © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Research
Nishi, Tatsuya
Takahashi, Hiroyuki
Hashimura, Miki
Yoshida, Tsutomu
Ohta, Yasutaka
Saegusa, Makoto
FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma
title FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma
title_full FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma
title_fullStr FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma
title_full_unstemmed FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma
title_short FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma
title_sort filgap, a rac-specific rho gtpase-activating protein, is a novel prognostic factor for follicular lymphoma
topic Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472203/
https://www.ncbi.nlm.nih.gov/pubmed/25641953
http://dx.doi.org/10.1002/cam4.423
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