Projects per year
Abstract
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.
Original language | English |
---|---|
Article number | e0185786 |
Number of pages | 23 |
Journal | PLoS ONE |
Volume | 12 |
Issue number | 10 |
DOIs | |
Publication status | Published - 2017 |
Keywords
- Animals
- Bone Marrow Cells
- Carcinoma, Lewis Lung
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Culture Media, Conditioned
- Dual Specificity Phosphatase 3
- Female
- Gene Deletion
- Hematopoietic Stem Cells
- Lung Neoplasms
- Macrophages
- Male
- Melanoma, Experimental
- Mice, Inbred C57BL
- Monocytes
- Journal Article
Fingerprint
Dive into the research topics of 'Dusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner'. Together they form a unique fingerprint.Projects
- 1 Finished
-
SRP47: Strategic Research Programme: Molecular Imaging and targeting of macrophages in Inflammation (ITARMI)
Lahoutte, T., Van Ginderachter, J. & Devoogdt, N.
1/11/17 → 31/10/22
Project: Fundamental