Dusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner

Maud Vandereyken, Sophie Jacques, Eva Van Overmeire, Mathieu Amand, Natacha Rocks, Céline Delierneux, Pratibha Singh, Maneesh Singh, Camille Ghuysen, Caroline Wathieu, Tinatin Zurashvili, Nor Eddine Sounni, Michel Moutschen, Christine Gilles, Cécile Oury, Didier Cataldo, Jo A Van Ginderachter, Souad Rahmouni

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 languageEnglish
Article numbere0185786
Number of pages23
JournalPLoS ONE
Volume12
Issue number10
DOIs
Publication statusPublished - 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

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