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Departments of Urology [H. L., P. M., Y. X., S. K., V. N., R. R., N. H. B.] and Cell Biology [A. K. R.], New York Hospital-Cornell Medical Center, New York, New York 10021, and the Ludwig Institute for Cancer Research, New York Branch, New York, New York 10021 [P. M., N. H. B.]
Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein expressed predominantly by prostate cancer cells. We have characterized four monoclonal antibodies that bind to the extracellular domain of PSMA (Liu et al., Cancer Res., 57: 3629–3634, 1997). Here we report that viable LNCaP cells internalize these antibodies. Laser scanning confocal microscopy reveals that the internalized antibodies accumulate in endosomes, and immunoelectron microscopy reveals that endocytosis of the PSMA-antibody complex occurs via clathrin-coated pits. In addition, a quantitative cell surface biotinylation assay demonstrates that PSMA is constitutively endocytosed in LNCaP cells and that anti-PSMA antibodies increase the rate of internalization of PSMA. These studies suggest that PSMA might function as a receptor mediating the internalization of a putative ligand. The availability of prostate-specific internalizing antibodies should aid the development of novel therapeutic methods to target the delivery of toxins, drugs, or short-range isotopes specifically to the interior of prostate cancer cells.
1 Supported by grants from The Association for the Cure of Cancer of the Prostate (CaP CURE), the David H. Koch Charitable Foundation, the Ronald P, and Susan E. Lynch Foundation, the Lawrence and Carol Zicklin Philanthropic Fund, the William T. Morris Foundation, the Bernice & Albert B. Cohen Philanthropic Fund through the Jewish Communal Fund, the John E. Wilson Research Fund, the Alissa Beth Bander Memorial Foundation, the Cornell Medical College Urological Oncology Research Fund, and BZL Biologics, Inc. N. H. B. is a consultant to BZL Biologics, Inc. N. H. B.'s agreement with BZL is managed by Cornell University in accordance with its conflict of interest policies.
2 H. L. and A. K. R. contributed equally to this work.
3 Present address: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA 90095.
4 To whom requests for reprints should be addressed, at New York Hospital-Cornell Medical Center, Box 23, 525 East 68th Street, New York, NY 10021. E-mail: nhbander@mail.med.cornell.edu.
Received 6/17/98. Accepted 7/31/98.
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