ADAM28 deletion in mice impacts lung metastasis formation

ADAM28 expression is upregulated in non-small cell lung carcinoma and correlated with cell proliferation and metastatic dissemination. In addition, ADAM28 is thought to be an important regulator of inflammatory signaling pathways as this protease shed the pro-inflammatory cytokine, pro-TNF-alpha. ADAM28 also interacts with integrins and a P-selectin ligand (PSGL-1) involved in inflammatory cell migration. All these findings suggest that ADAM28 contributes to cancer development and progression.This project aims to characterize the effects of host-derived ADAM28 on lung metastasis formation using an ADAM28-/- mouse model.Lewis Lung Carcinoma cells and B16K1 melanoma cells were intravenously injected in ADAM28-/- and wild-type (WT) mice. An unexpected increased tumor development was found in lungs of ADAM28-/- mice. As ADAM28 is associated with lymphocyte transendothelial migration, lymphocyte subtypes implicated in tumor cytotoxicity or in regulation of immune response were studied by flow cytometry. Results showed that less CD8+ T and NK cells were infiltrated within lungs of ADAM28-/- tumor-bearing mice as compared to WT mice. Moreover, less CD8+ T cells were counted within the spleen of naïve ADAM28-/- mice. These data were confirmed in a mouse model where 4T1 breast carcinoma cells were intravenously injected in ADAM28-/- BALB/c mice. Intrinsic properties of CD8+ T cells from ADAM28-/- mice were not affected by ADAM28 depletion as they were able to proliferate, to b...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Lung Cancer Source Type: research