PMID- 29020102 OWN - NLM STAT- MEDLINE DCOM- 20171023 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 10 DP - 2017 TI - Dusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner. PG - e0185786 LID - 10.1371/journal.pone.0185786 [doi] LID - e0185786 AB - Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion prevents neo-angiogenesis and b-FGF-induced microvessel outgrowth. Considering the importance of angiogenesis in metastasis formation, our study aimed to investigate the role of DUSP3 in tumour cell dissemination. Using a Lewis Lung carcinoma (LLC) experimental metastasis model, we observed that DUSP3-/- mice developed larger lung metastases than littermate controls. DUSP3-/- bone marrow transfer to lethally irradiated DUSP3+/+ mice was sufficient to transfer the phenotype to DUSP3+/+ mice, indicating that hematopoietic cells compartment was involved in the increased tumour cell dissemination to lung tissues. Interestingly, we found a higher percentage of tumour-promoting Ly6Cint macrophages in DUSP3-/- LLC-bearing lung homogenates that was at least partially due to a better recruitment of these cells. This was confirmed by 1) the presence of higher number of the Ly6Bhi macrophages in DUSP3-/- lung homogenates and by 2) the better migration of DUSP3-/- bone marrow sorted monocytes, peritoneal macrophages and bone marrow derived macrophages (BMDMs), compared to DUSP3+/+ monocytes, macrophages and BMDMs, in response to LLC-conditioned medium. Our study demonstrates that DUSP3 phosphatase plays a key role in metastatic growth through a mechanism involving the recruitment of macrophages towards LLC-bearing lungs. FAU - Vandereyken, Maud AU - Vandereyken M AD - Immunology and Infectious Disease Unit, GIGA-I3, University of Liege, Liege, Belgium. FAU - Jacques, Sophie AU - Jacques S AD - Immunology and Infectious Disease Unit, GIGA-I3, University of Liege, Liege, Belgium. FAU - Van Overmeire, Eva AU - Van Overmeire E AD - Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium. AD - Laboratory of Myeloid Cell Immunology, VIB inflammation research center, Ghent, Belgium. FAU - Amand, Mathieu AU - Amand M AD - Immunology and Infectious Disease Unit, GIGA-I3, University of Liege, Liege, Belgium. FAU - Rocks, Natacha AU - Rocks N AD - Laboratory of Tumour and Developmental Biology, GIGA-Cancer, University of Liege, Liege, Belgium. FAU - Delierneux, Celine AU - Delierneux C AD - Laboratory of Thrombosis and Haemostasis, GIGA-Cardiovascular Sciences Unit, University of Liege, Liege, Belgium. FAU - Singh, Pratibha AU - Singh P AD - Immunology and Infectious Disease Unit, GIGA-I3, University of Liege, Liege, Belgium. FAU - Singh, Maneesh AU - Singh M AD - Immunology and Infectious Disease Unit, GIGA-I3, University of Liege, Liege, Belgium. FAU - Ghuysen, Camille AU - Ghuysen C AD - Immunology and Infectious Disease Unit, GIGA-I3, University of Liege, Liege, Belgium. FAU - Wathieu, Caroline AU - Wathieu C AD - Immunology and Infectious Disease Unit, GIGA-I3, University of Liege, Liege, Belgium. FAU - Zurashvili, Tinatin AU - Zurashvili T AD - Immunology and Infectious Disease Unit, GIGA-I3, University of Liege, Liege, Belgium. FAU - Sounni, Nor Eddine AU - Sounni NE AD - Laboratory of Tumour and Developmental Biology, GIGA-Cancer, University of Liege, Liege, Belgium. FAU - Moutschen, Michel AU - Moutschen M AD - Immunology and Infectious Disease Unit, GIGA-I3, University of Liege, Liege, Belgium. FAU - Gilles, Christine AU - Gilles C AD - Laboratory of Tumour and Developmental Biology, GIGA-Cancer, University of Liege, Liege, Belgium. FAU - Oury, Cecile AU - Oury C AD - Laboratory of Thrombosis and Haemostasis, GIGA-Cardiovascular Sciences Unit, University of Liege, Liege, Belgium. FAU - Cataldo, Didier AU - Cataldo D AD - Laboratory of Tumour and Developmental Biology, GIGA-Cancer, University of Liege, Liege, Belgium. FAU - Van Ginderachter, Jo A AU - Van Ginderachter JA AD - Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium. AD - Laboratory of Myeloid Cell Immunology, VIB inflammation research center, Ghent, Belgium. FAU - Rahmouni, Souad AU - Rahmouni S AUID- ORCID: 0000-0003-0956-0242 AD - Immunology and Infectious Disease Unit, GIGA-I3, University of Liege, Liege, Belgium. LA - eng PT - Journal Article DEP - 20171011 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Culture Media, Conditioned) RN - EC 3.1.3.48 (Dual Specificity Phosphatase 3) RN - EC 3.1.3.48 (Dusp3 protein, mouse) SB - IM MH - Animals MH - Bone Marrow Cells/drug effects/pathology MH - Carcinoma, Lewis Lung/pathology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Culture Media, Conditioned/pharmacology MH - Dual Specificity Phosphatase 3/*metabolism MH - Female MH - *Gene Deletion MH - Hematopoietic Stem Cells/drug effects/metabolism MH - Lung Neoplasms/pathology/*secondary MH - Macrophages/drug effects/*pathology MH - Male MH - Melanoma, Experimental/pathology MH - Mice, Inbred C57BL MH - Monocytes/drug effects/pathology PMC - PMC5636116 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/10/12 06:00 MHDA- 2017/10/24 06:00 PMCR- 2017/10/11 CRDT- 2017/10/12 06:00 PHST- 2017/03/15 00:00 [received] PHST- 2017/09/19 00:00 [accepted] PHST- 2017/10/12 06:00 [entrez] PHST- 2017/10/12 06:00 [pubmed] PHST- 2017/10/24 06:00 [medline] PHST- 2017/10/11 00:00 [pmc-release] AID - PONE-D-17-10201 [pii] AID - 10.1371/journal.pone.0185786 [doi] PST - epublish SO - PLoS One. 2017 Oct 11;12(10):e0185786. doi: 10.1371/journal.pone.0185786. eCollection 2017.