A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits spontaneous pulmonary metastasis of osteosarcoma cells in vivo.
OBJECTIVE
The melanoma cellular adhesion molecule, also known as MUC18, is highly expressed on several tumors, including bone sarcomas. The level of MUC18 expression has been found to correlate directly with tumor progression and metastatic potential. These observations have established MUC18 as a candidate mediator of tumor growth and metastasis, and suggest that blockade of MUC18 might be a potential target for immunotherapy against several MUC18-expressing tumors, including human bone sarcomas.


METHODS
To investigate whether blockade of MUC18 might be a potential target for immunotherapy against osteosarcoma, we have recently developed a fully human anti-MUC18 antibody, ABX-MA1. We studied the effect of ABX-MA1 on growth, adhesion, invasion, and metastasis of human osteosaroma cells both in vitro and in vivo.


RESULTS
MUC18 was widely expressed on both osteosarcoma and Ewing's sarcoma cells. ABX-MA1 had no effect on the proliferation of osteosarcoma cells in vitro, nor did it significantly inhibit the growth of KRIB human osteosarcoma cells when they were orthotopically implanted into the tibias of nude mice. However, after 6 weeks, significantly fewer ABX-MA1-treated mice developed spontaneous pulmonary metastases than did IgG-treated control mice. Additionally, ABX-MA1 decreased the invasion of osteosarcoma cells through Matrigel-coated filters and disrupted homotypic adhesion between osteosarcoma cells and their heterotypic interaction with human vascular endothelial cells.


CONCLUSIONS
Our findings demonstrate that MUC18 plays a central role in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by ABX-MA1 may be a novel immunotherapeutic approach in the management of this tumor.
McGary
Eric C
EC
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77054, USA.
Heimberger
Amy
A
Mills
Lisa
L
Weber
Kristy
K
Thomas
Gary W
GW
Shtivelband
Mikhail
M
Lev
Dina Chelouche
DC
Bar-Eli
Menashe
M
D000818:Animals; D015703:Antigens, CD; D015153:Blotting, Western; D001842:Bone and Bones / Q000473:pathology; D051929:CD146 Antigen; D002448:Cell Adhesion; D002455:Cell Division; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D018450:Disease Progression; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D007797:Laminin / Q000494:pharmacology; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019006:Neural Cell Adhesion Molecules; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000494:pharmacology; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D051929:CD146 Antigen; D004338:Drug Combinations; D007074:Immunoglobulin G; D007797:Laminin; C497902:MCAM protein, human; C497903:Mcam protein, mouse; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen