Transient resistance to B16F10 melanoma growth and metastasis in CD43-/- mice.
CD43, the major transmembrane sialoglycoprotein of neutrophils, monocytes, T lymphocytes and platelets, is highly glycosylated and its high sialic acid content contributes to the strongly negative charge of cells. In this study the role of CD43 in melanoma development was addressed using CD43 -/- mice (null mutated for the corresponding gene or knockout [KO]). Growth of B16F10 melanoma was retarded in the KO mice compared with the wild-type CD43+/+ control (WT). A marked difference in lung colonization and other metastatic foci was observed in the KO and WT mice up to 15 days after intravenous injection of tumour cells. The initial resistance of KO mice was reversed with time, and in the long term there was no difference in the survival rate of the two animal groups. Transient resistance was attributed to increased adhesion of thrombin-activated platelets and leukocytes to melanoma and endothelial cells in KO mice. In the KO mice tumour emboli were found in the central portion of the lung more than at the lung periphery immediately after intravenous injection, in contrast to the WT mice. Activation of melanoma adhesion receptors by thrombin or TRAP stimulated lung colonization in WT but not KO mice. Therefore, the correlation of tumour embolism and metastasis in short-term experiments depends on the nature and stability of interactions between the tumour and the blood/endothelial cells of the host.
Fuzii
H T
HT
Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Brazil.
Travassos
L R
LR
D000818:Animals; D015703:Antigens, CD; D001792:Blood Platelets / Q000378:metabolism; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology; D051917:Leukosialin; D008168:Lung / Q000473:pathology; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D015539:Platelet Activation; D012794:Sialic Acids / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051917:Leukosialin; D012794:Sialic Acids; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D013917:Thrombin