Cargando…
M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma
Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly su...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964568/ https://www.ncbi.nlm.nih.gov/pubmed/27464733 http://dx.doi.org/10.1038/srep30347 |
_version_ | 1782445139910721536 |
---|---|
author | Shen, Long Li, Honghao Shi, Yuzhi Wang, Dekun Gong, Junbo Xun, Jing Zhou, Sifan Xiang, Rong Tan, Xiaoyue |
author_facet | Shen, Long Li, Honghao Shi, Yuzhi Wang, Dekun Gong, Junbo Xun, Jing Zhou, Sifan Xiang, Rong Tan, Xiaoyue |
author_sort | Shen, Long |
collection | PubMed |
description | Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells. Moreover, M2 polarization of macrophages induced legumain expression in U937 cells. Exogenous legumain promoted degradation of fibronectin and collagen I, which was abolished by administration of a legumain inhibitor RR-11a. Overexpression of legumain in Raw 264.7 cells also induced tube formation of endothelial cells in matrigel. In the xenograft mouse model of DLBCL, decreased fibronectin and collagen I, as well as increased legumain expression and angiogenesis were found at the late stage tumours compared with early stage tumours. Co-localization of legumain and fibronectin was observed in the extracellular matrix of tumour tissues. Administration of the legumain inhibitor to the xenograft DLBCL model suppressed tumour growth, angiogenesis and collagen deposition compared with the control. Taken together, our results suggest that M2 tumour-associated macrophages affect degradation of the extracellular matrix and angiogenesis via overexpression of legumain, and therefore play an active role in the progression of DLBCL. |
format | Online Article Text |
id | pubmed-4964568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49645682016-08-08 M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma Shen, Long Li, Honghao Shi, Yuzhi Wang, Dekun Gong, Junbo Xun, Jing Zhou, Sifan Xiang, Rong Tan, Xiaoyue Sci Rep Article Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells. Moreover, M2 polarization of macrophages induced legumain expression in U937 cells. Exogenous legumain promoted degradation of fibronectin and collagen I, which was abolished by administration of a legumain inhibitor RR-11a. Overexpression of legumain in Raw 264.7 cells also induced tube formation of endothelial cells in matrigel. In the xenograft mouse model of DLBCL, decreased fibronectin and collagen I, as well as increased legumain expression and angiogenesis were found at the late stage tumours compared with early stage tumours. Co-localization of legumain and fibronectin was observed in the extracellular matrix of tumour tissues. Administration of the legumain inhibitor to the xenograft DLBCL model suppressed tumour growth, angiogenesis and collagen deposition compared with the control. Taken together, our results suggest that M2 tumour-associated macrophages affect degradation of the extracellular matrix and angiogenesis via overexpression of legumain, and therefore play an active role in the progression of DLBCL. Nature Publishing Group 2016-07-28 /pmc/articles/PMC4964568/ /pubmed/27464733 http://dx.doi.org/10.1038/srep30347 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Shen, Long Li, Honghao Shi, Yuzhi Wang, Dekun Gong, Junbo Xun, Jing Zhou, Sifan Xiang, Rong Tan, Xiaoyue M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma |
title | M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma |
title_full | M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma |
title_fullStr | M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma |
title_full_unstemmed | M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma |
title_short | M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma |
title_sort | m2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large b cell lymphoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964568/ https://www.ncbi.nlm.nih.gov/pubmed/27464733 http://dx.doi.org/10.1038/srep30347 |
work_keys_str_mv | AT shenlong m2tumourassociatedmacrophagescontributetotumourprogressionvialegumainremodellingtheextracellularmatrixindiffuselargebcelllymphoma AT lihonghao m2tumourassociatedmacrophagescontributetotumourprogressionvialegumainremodellingtheextracellularmatrixindiffuselargebcelllymphoma AT shiyuzhi m2tumourassociatedmacrophagescontributetotumourprogressionvialegumainremodellingtheextracellularmatrixindiffuselargebcelllymphoma AT wangdekun m2tumourassociatedmacrophagescontributetotumourprogressionvialegumainremodellingtheextracellularmatrixindiffuselargebcelllymphoma AT gongjunbo m2tumourassociatedmacrophagescontributetotumourprogressionvialegumainremodellingtheextracellularmatrixindiffuselargebcelllymphoma AT xunjing m2tumourassociatedmacrophagescontributetotumourprogressionvialegumainremodellingtheextracellularmatrixindiffuselargebcelllymphoma AT zhousifan m2tumourassociatedmacrophagescontributetotumourprogressionvialegumainremodellingtheextracellularmatrixindiffuselargebcelllymphoma AT xiangrong m2tumourassociatedmacrophagescontributetotumourprogressionvialegumainremodellingtheextracellularmatrixindiffuselargebcelllymphoma AT tanxiaoyue m2tumourassociatedmacrophagescontributetotumourprogressionvialegumainremodellingtheextracellularmatrixindiffuselargebcelllymphoma |