TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells
Abstract Background Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. Methods To specifically test the i...
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doaj-f560872f34c64405b7258d44b284a3e72020-12-13T12:39:56ZengBMCBMC Cancer1471-24072019-12-0119111410.1186/s12885-019-6429-zTIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cellsChristian Benzing0Hoyin Lam1Chi Man Tsang2Alexander Rimmer3Yoana Arroyo-Berdugo4Yolanda Calle5Claire M. Wells6School of Cancer and Pharmaceutical Sciences, New Hunts House, Kings College LondonSchool of Cancer and Pharmaceutical Sciences, New Hunts House, Kings College LondonDepartment of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong KongSchool of Cancer and Pharmaceutical Sciences, New Hunts House, Kings College LondonDepartment of Life Sciences, University of RoehamptonDepartment of Life Sciences, University of RoehamptonSchool of Cancer and Pharmaceutical Sciences, New Hunts House, Kings College LondonAbstract Background Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. Methods To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay. Results Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity. Conclusions Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC.https://doi.org/10.1186/s12885-019-6429-zPancreatic ductal adenocarcinomaMonocytesTumor microenvironmentTIMP2Invadopodia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christian Benzing Hoyin Lam Chi Man Tsang Alexander Rimmer Yoana Arroyo-Berdugo Yolanda Calle Claire M. Wells |
spellingShingle |
Christian Benzing Hoyin Lam Chi Man Tsang Alexander Rimmer Yoana Arroyo-Berdugo Yolanda Calle Claire M. Wells TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells BMC Cancer Pancreatic ductal adenocarcinoma Monocytes Tumor microenvironment TIMP2 Invadopodia |
author_facet |
Christian Benzing Hoyin Lam Chi Man Tsang Alexander Rimmer Yoana Arroyo-Berdugo Yolanda Calle Claire M. Wells |
author_sort |
Christian Benzing |
title |
TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells |
title_short |
TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells |
title_full |
TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells |
title_fullStr |
TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells |
title_full_unstemmed |
TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells |
title_sort |
timp-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2019-12-01 |
description |
Abstract Background Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. Methods To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay. Results Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity. Conclusions Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC. |
topic |
Pancreatic ductal adenocarcinoma Monocytes Tumor microenvironment TIMP2 Invadopodia |
url |
https://doi.org/10.1186/s12885-019-6429-z |
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