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Inhibition of Human Melanoma Growth and Metastasis in Vivo by Anti-CD44 Monoclonal Antibody¹

Institute of Pathology, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 [Y. G., J. M., X. C., M-S. S.]; Institute of Hepatobiliary Surgery, Changhai Hospital, Shanghai 200433, People's Republic of China [Y. G., X. C., M. W.]; and Departments of Dermatology [J. W., M. B.] and Radiology [J. N.], Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

CD44 is a M_r 90,000 surface glycoprotein believed to be involved in cell adhesion and migration. We investigated the role of CD44 in tumor growth and metastasis using human melanoma cell lines SMMU-1 and SMMU-2. Both SMMU-1 and SMMU-2 form tumors in the s.c. tissues when injected s.c. in SCID mice but only SMMU-2 metastasizes. Approximately one-half of SCID mice receiving injections of SMMU-2 s.c. develop metastatic tumors. SMMU-2 but not SMMU-1 expresses high levels of the hematopoietic form of CD44 and binds fluorescence-conjugated hyaluronic acid in vitro.

GKW.A3 is a monoclonal antibody specific for human CD44 that can completely inhibit the binding of hyaluronic acid to SMMU-2 tumor cells in vitro. Moreover, in vivo injection of GKW.A3 inhibited the growth and metastatic potential of SMMU-2 tumor cells. Administration of GKW.A3 i.v. 1 week after s.c. tumor injection did not inhibit local tumor development but inhibited the formation of metastatic tumors and prolonged animal survival. Therefore, interactions between CD44 on tumor cells and its ligands in vivo may be necessary for tumor growth and metastasis.

¹ This work was supported in part by Grants RO-1 AI-277740, AR-38018, and AR39795 from NIH and a Visiting Chinese Scholarship from Science Philosophy Betterment Society. Y.J.G. is a recipient of the International Exchange Research Award from China Nature & Science Foundation.

² To whom all requests for reprints should be addressed, at Institute of Pathology, Case Western Reserve University, Biomedical Research Building, Room 947, 10900 Euclid Avenue, Cleveland, Ohio 44106-4943.

Received 9/16/93. Accepted 1/17/94.

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