Microenvironment-derived ADAM28 prevents cancer dissemination

Abstract

Previous studies have linked cancer cell-associated ADAM28 expression with tumor progression and metastatic dissemination. However, the role of host-derived ADAM28 in cancer dissemination processes remains unclear. Genetically engineered-mice fully deficient for ADAM28 unexpectedly display increased lung colonization by pulmonary, melanoma or breast tumor cells. In experimental tumor cell dissemination models, host ADAM28 deficiency is further associated with a decreased lung infiltration by CD8⁺ T lymphocytes. Notably, naive ADAM28-deficient mice already display a drastic reduction of CD8⁺ T cells in spleen which is further observed in lungs. Interestingly, <i>ex vivo</i> CD8⁺ T cell characterization revealed that ADAM28-deficiency does not impact proliferation, migration nor activation of CD8⁺ T cells. Our data highlight a functional role of ADAM28 in T cell mobilization and point to an unexpected protective role for host ADAM28 against metastasis.