Blocking of lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) inhibits murine melanoma lung metastasis.
The 90-kD lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) selectively promotes Ca(2+)-dependent adhesion of lung-metastatic B16 melanoma cells. Corresponding with their metastatic performance, high lung-metastatic B16-F10 melanoma cells bind in significantly higher numbers to Lu-ECAM-1 than their intermediate and low lung-metastatic counterparts B16-L8-F10 and B16-F0, respectively. Maximum attachment is observed at a density of approximately 2.4 x 10(2) Lu-ECAM-1 sites/microns2 of plastic surface. B16 melanoma cell binding to Lu-ECAM-1 is blocked by mAb 6D3 and is competitively inhibited by soluble Lu-ECAM-1. C57B1/6 mice passively immunized with anti-Lu-ECAM-1 mAb 6D3 or actively immunized with purified Lu-ECAM-1 exhibit an anti-Lu-ECAM-1 antibody titer-dependent reduction in the number of B16 experimental metastases. Lu-ECAM-1 promotes neither binding nor metastasis of other lung-metastatic tumor cells (e.g., KLN205). Our data indicate that an "antiadhesion" therapy directed at interfering with the adherence of blood-borne tumor cells to organ-specific vascular endothelium is efficient in the control of metastasis formation in selective organ sites.
Zhu
D
D
Department of Pathology, Cornell University College of Veterinary Medicine, Ithaca, New York 14853.
Cheng
C F
CF
Pauli
B U
BU
D000818:Animals; D000906:Antibodies; D001667:Binding, Competitive; D002417:Cattle; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology*; D008175:Lung Neoplasms / Q000517:prevention & control*; D008545:Melanoma / Q000556:secondary* / Q000628:therapy; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control; D014407:Tumor Cells, Cultured; D014611:Vaccination
D000906:Antibodies; D015815:Cell Adhesion Molecules; C071433:Lu-ECAM-1 protein, Bos taurus