Synergistic defense system by cooperative natural effectors against metastasis of B16 melanoma cells in H-2-associated control: different behavior of H-2+ and H-2- cells in metastatic processes.
H-2+ and H-2- cells of B16 melanoma were established by repeated fluorescence-activated cell sorting. The H-2- line formed no metastasis in untreated C57BL/6 mice, whereas the H-2+ cells showed evidence of metastatic development. This difference was ascribed mainly to the increased susceptibility of H-2- cells to attack by natural effector mechanisms, particularly asialo GM1+ NK cells. After treatment with both anti-asialo GM1 serum and whole body irradiation (400 rad), numerous colonies of H-2- cells formed in the lung, whereas the metastasis was only marginally enhanced by irradiation and moderately by treatment with anti-asialo GM1 serum. With the H-2+ cells, treatment with each modality significantly increased the number of metastatic colonies. Therefore collaboration of asialo GM1+ NK cells and radiosensitive natural effectors seems to be the main mechanism involved in the synergistic effects on defense against H-2- cell metastasis, and to a lesser extent against H-2+ cell metastasis. Irradiation (1000 rad) to the right lung to abrogate the organ-associated defense increased the colonies, particularly in the H-2+ cells. On the other hand, treatment with anti-asialo GM1 serum increased colonization in the early phase of metastasis with H-2- cells and may have abolished asialo GM1+ NK cells capable of recognizing the reduced expression of H-2 antigens and eliminating H-2- cells in the blood-born phase. Natural defense mechanisms probably exert suppressive effects on the metastasis of H-2+ cells, mainly in the organ-associated phase after extravasation.
Y
Y
Kawano
K
K
Taniguchi
A
A
Toshitani
K
K
Nomoto
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D005260:Female; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000276:immunology; D006183:H-2 Antigens / Q000032:analysis / Q000276:immunology*; D007106:Immune Sera / Q000008:administration & dosage; D007116:Immunization, Passive; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000528:radiation effects / Q000637:transplantation; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary; D008207:Lymphatic Metastasis / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000528:radiation effects; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013154:Spleen
D006028:Glycosphingolipids; D006183:H-2 Antigens; D007106:Immune Sera; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside