Regulation of local and metastatic host-mediated anti-tumour mechanisms by L-selectin and intercellular adhesion molecule-1.
Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules, including L-selectin and intercellular adhesion molecule-1 (ICAM-1), in this process, subcutaneous primary growth and metastasis to the lung of B16 melanoma cells not expressing L-selectin, ICAM-1 or their ligands were examined in mice lacking L-selectin, ICAM-1 or both. Primary subcutaneous growth of B16 melanoma was augmented by loss of L-selectin, ICAM-1 or both, while pulmonary metastasis was enhanced by the loss of L-selectin or combined loss of L-selectin and ICAM-1. In both situations, the combined loss of L-selectin and ICAM-1 exhibited the greatest effect. This enhancement was associated generally with a reduced accumulation of natural killer (NK) cells, CD4+ T cells and CD8+ T cells and also with a diminished release of interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha but not interleukin (IL)-6. Cytotoxicity against melanoma was not defective by the absence of ICAM-1, L-selectin or both, suggesting that the enhancement of tumour growth and metastasis caused by the loss of adhesion molecules results from an impaired migration of effector cells into the tissue rather than from a suppression of the cytotoxic response. The results indicate that L-selectin and ICAM-1 contribute co-operatively to the anti-tumour reaction by regulating lymphocyte infiltration to the tumour.
Yamada
M
M
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
Yanaba
K
K
Hasegawa
M
M
Matsushita
Y
Y
Horikawa
M
M
Komura
K
K
Matsushita
T
T
Kawasuji
A
A
Fujita
T
T
Takehara
K
K
Steeber
D A
DA
Tedder
T F
TF
Sato
S
S
D000818:Animals; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D019041:L-Selectin / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D008175:Lung Neoplasms / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin