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.
van Nimwegen
Maroesja J
MJ
Division of Toxicology, Leiden Amsterdam Center for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.
Verkoeijen
Saertje
S
Kuppen
Peter J K
PJ
Velthuis
Jurjen H L
JH
van de Water
Bob
B
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D053804:Granzymes / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007113:Immunity, Innate; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary; D008213:Lymphocyte Activation; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology; D009368:Neoplasm Transplantation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014183:Transplantation, Heterologous
D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D053804:Granzymes; D053148:Caspase 3