Mediation of lung metastasis of murine melanomas by a lung-specific endothelial cell adhesion molecule.
Organ-specific adhesion molecules expressed by vascular endothelial cells have been implicated in the arrest of blood-borne cancer cells in selective, secondary sites. A lung-specific endothelial cell adhesion molecule (Lu-ECAM-1) localized on endothelia of distinct branches of lung blood vessels has been purified by immunoaffinity chromatography from detergent extracts of lung matrix-modulated endothelial cells using monoclonal antibody (mAb) 6D3. It has a molecular mass of 90 kDa and promotes the selective attachment of lung-metastatic B16 melanoma cells. Corresponding with their metastatic performance, B16-F10 tumor cells selected for higher lung colonization bind to Lu-ECAM-1 in significantly higher numbers than their low lung metastatic counterpart B16-F0. Binding of B16-F0 and B16-F10 is reduced with mAb 6D3 to slightly lower levels than B16-F0 bound to Lu-ECAM-1. mAb 6D3 injected into C57BL/6 mice 1 hr prior to an i.v. challenge with B16-F10 causes a 90% reduction in the number of lung colonies compared with animals injected with control mAb (6D8 or 3C6). Lu-ECAM-1 neither binds nor effects metastasis of other lung-colonizing tumor cells (e.g., KLN205). Thus, site-specific metastasis of tumor cells is regulated by similar mechanisms as the homing of lymphocytes--namely, by the ability of blood-borne cancer cells to recognize and adhere to distinct endothelial cell adhesion molecules.
Zhu
D Z
DZ
Department of Pathology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853.
Cheng
C F
CF
Pauli
B U
BU
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; C071433:Lu-ECAM-1 protein, Bos taurus