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

[en] 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 out- growth. 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 devel- oped 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 pres- ence 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 demon- strates that DUSP3 phosphatase plays a key role in metastatic growth through a mechanism involving the recruitment of macrophages towards LLC-bearing lungs.

Disciplines :

Oncology

Author, co-author :

Vandereyken, Maud

Jacques, Sophie ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.

Van Overmeire, Eva

Amand, Mathieu

Rocks, Natacha ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique

Delierneux, Celine

Singh, Pratibha

Singh, MAneesh

GHUYSEN, Camille ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service d'oncologie médicale

Wathieu, Caroline ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

More authors (8 more)

Language :

English

Title :

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

Publication date :

11 October 2017

Journal title :

PLoS ONE

eISSN :

1932-6203

Publisher :

Public Library of Science, San Franscisco, United States - California

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 12 November 2017

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