An improved method to study NK-independent mechanisms of MTLn3 breast cancer lung metastasis

To study the tumor cell autonomous processes of metastasis, an in vivo tumor metastasis model is required that excludes the involvement of the innate immune system. For this purpose we used the established syngeneic MTLn3 cell – Fischer 344 tumor model. MTLn3 cells are efficiently eradicated by NK cells in vivo. Using isolated cell systems, we provide evidence for apoptosis-induction by IL-2 activated NK cells, but not T-cells, despite the expression of MHC class I. This is largely mediated by the perforin/granzyme B pathway in MTLn3 cells in a caspase-dependent manner. Temporal in vivo depletion of NK cells by an antibody-based method, dramatically improved colonization of the lungs by MTLn3 cells, from 5 metastases in the untreated animals to 130 metastases in the NK-depleted animals. Thus, we improved the syngeneic MTLn3-Fischer 344 tumor model by temporal depletion of NK cells of which the advantages over the use of immunodeficient animals are evident.