Cargando…
Tumour cell-derived debris and IgG synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages
BACKGROUND: The progression and metastasis of pancreatic ductal adenocarcinoma (PDAC) is highly dependent on the tumour microenvironment. Most tumour-associated macrophages (TAMs) are M2 phenotype macrophages, which normally show anti-inflammatory functions in numerous disorders. Previously, we foun...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889176/ https://www.ncbi.nlm.nih.gov/pubmed/31588122 http://dx.doi.org/10.1038/s41416-019-0595-2 |
_version_ | 1783475361206501376 |
---|---|
author | Chen, Qi Wang, Jianxin Zhang, Qi Zhang, Jingying Lou, Yu Yang, Jiaqi Chen, Yiwen Wei, Tao Zhang, Jian Fu, Qihan Ye, Mao Zhang, Xiaozhen Dang, Xiaowei Liang, Tingbo Bai, Xueli |
author_facet | Chen, Qi Wang, Jianxin Zhang, Qi Zhang, Jingying Lou, Yu Yang, Jiaqi Chen, Yiwen Wei, Tao Zhang, Jian Fu, Qihan Ye, Mao Zhang, Xiaozhen Dang, Xiaowei Liang, Tingbo Bai, Xueli |
author_sort | Chen, Qi |
collection | PubMed |
description | BACKGROUND: The progression and metastasis of pancreatic ductal adenocarcinoma (PDAC) is highly dependent on the tumour microenvironment. Most tumour-associated macrophages (TAMs) are M2 phenotype macrophages, which normally show anti-inflammatory functions in numerous disorders. Previously, we found that alternatively activated macrophages showed pro-inflammatory characteristics upon stimulation with hepatoma cell-derived debris; however, the molecular mechanism was unclear. METHODS: In vitro and in vivo experiments were employed to investigate the molecular mechanism. Using pancreatic cancer cell lines, mouse models and human tissues, we obtained a general picture of tumour cell-derived debris promoting metastasis of pancreatic cancer by inducing inflammation via TAMs. RESULTS: We showed that M2 macrophage-derived inflammation also exists in PDAC. Debris from PDAC cells induced potent IL-1β release by M2 macrophages via TLR4/TRIF/NF-κB signalling, and this effect was further boosted by IgG that was also derived from PDAC cells. Increased IL-1β promoted epithelial–mesenchymal transition and consequent metastasis of PDAC cells. A selective COX-2 inhibitor, celecoxib, enhanced the anti-tumoural efficacy of gemcitabine. CONCLUSIONS: These data revealed a pro-inflammatory mechanism in PDAC, which indicated that IL-1β and COX-2 could be therapeutic targets of an anti-inflammatory strategy to treat PDAC. |
format | Online Article Text |
id | pubmed-6889176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68891762019-12-04 Tumour cell-derived debris and IgG synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages Chen, Qi Wang, Jianxin Zhang, Qi Zhang, Jingying Lou, Yu Yang, Jiaqi Chen, Yiwen Wei, Tao Zhang, Jian Fu, Qihan Ye, Mao Zhang, Xiaozhen Dang, Xiaowei Liang, Tingbo Bai, Xueli Br J Cancer Article BACKGROUND: The progression and metastasis of pancreatic ductal adenocarcinoma (PDAC) is highly dependent on the tumour microenvironment. Most tumour-associated macrophages (TAMs) are M2 phenotype macrophages, which normally show anti-inflammatory functions in numerous disorders. Previously, we found that alternatively activated macrophages showed pro-inflammatory characteristics upon stimulation with hepatoma cell-derived debris; however, the molecular mechanism was unclear. METHODS: In vitro and in vivo experiments were employed to investigate the molecular mechanism. Using pancreatic cancer cell lines, mouse models and human tissues, we obtained a general picture of tumour cell-derived debris promoting metastasis of pancreatic cancer by inducing inflammation via TAMs. RESULTS: We showed that M2 macrophage-derived inflammation also exists in PDAC. Debris from PDAC cells induced potent IL-1β release by M2 macrophages via TLR4/TRIF/NF-κB signalling, and this effect was further boosted by IgG that was also derived from PDAC cells. Increased IL-1β promoted epithelial–mesenchymal transition and consequent metastasis of PDAC cells. A selective COX-2 inhibitor, celecoxib, enhanced the anti-tumoural efficacy of gemcitabine. CONCLUSIONS: These data revealed a pro-inflammatory mechanism in PDAC, which indicated that IL-1β and COX-2 could be therapeutic targets of an anti-inflammatory strategy to treat PDAC. Nature Publishing Group UK 2019-10-07 2019-10-29 /pmc/articles/PMC6889176/ /pubmed/31588122 http://dx.doi.org/10.1038/s41416-019-0595-2 Text en © The Author(s) 2019 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chen, Qi Wang, Jianxin Zhang, Qi Zhang, Jingying Lou, Yu Yang, Jiaqi Chen, Yiwen Wei, Tao Zhang, Jian Fu, Qihan Ye, Mao Zhang, Xiaozhen Dang, Xiaowei Liang, Tingbo Bai, Xueli Tumour cell-derived debris and IgG synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages |
title | Tumour cell-derived debris and IgG synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages |
title_full | Tumour cell-derived debris and IgG synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages |
title_fullStr | Tumour cell-derived debris and IgG synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages |
title_full_unstemmed | Tumour cell-derived debris and IgG synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages |
title_short | Tumour cell-derived debris and IgG synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages |
title_sort | tumour cell-derived debris and igg synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889176/ https://www.ncbi.nlm.nih.gov/pubmed/31588122 http://dx.doi.org/10.1038/s41416-019-0595-2 |
work_keys_str_mv | AT chenqi tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT wangjianxin tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT zhangqi tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT zhangjingying tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT louyu tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT yangjiaqi tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT chenyiwen tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT weitao tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT zhangjian tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT fuqihan tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT yemao tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT zhangxiaozhen tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT dangxiaowei tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT liangtingbo tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages AT baixueli tumourcellderiveddebrisandiggsynergisticallypromotemetastasisofpancreaticcancerbyinducinginflammationviatumourassociatedmacrophages |