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Consistent Expression of an Epithelial Cell Adhesion Molecule (C-CAM) during Human Prostate Development and Loss of Expression in Prostate Cancer: Implication as a Tumor Suppressor¹

Departments of Urology [D. I. K., L. L. P., A. C. v. E., J-T. H.], Molecular Pathology [S-H. L.], Pathology [P. T., T. B.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611 [E. R. S.]

Cell adhesion molecules have been suggested to function as tumor suppressor molecules. We have been studying one of the epithelial cell adhesion molecules (C-CAM), which belongs to the immunoglobulin gene superfamily. Transfection of a C-CAM cDNA expression vector into a highly tumorigenic human prostate cancer cell line (PC-3) suppresses tumor formation in nude mice. Alternatively, reducing C-CAM expression levels in the nontumorigenic rat prostate epithelial cell line NbE by the antisense expression vector markedly increases tumorigenicity of NbE cells in nude mice. These results suggest that C-CAM may be a tumor suppressor in prostate cancer.

In this study, we examined the relationship between C-CAM expression during human prostate development and neoplastic progression by immunohistochemical staining of frozen sections. C-CAM predominantly localized on the plasma membrane of the basal cell layer in both the fetal and normal adult prostate gland. However, an overall decreased staining was seen in benign prostatic hyperplasia and high grade prostatic intraepithelial neoplasia. Furthermore, C-CAM was not detected in prostate carcinomas. Thus, a decrease in C-CAM expression may be an early event in hyperplastic/neoplastic transformation. These observations support the suggestion that C-CAM is a tumor suppressor in prostate cancer progression.

¹ Supported by an American Cancer Society Clinical Oncology Fellowship (D. I. K.) and NIH Grants GM 43189 (S-H. L.) and CA59939 (J-T. H.).

² To whom requests for reprints should be addressed, at the Department of Urology, Box 026, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 11/15/94. Accepted 2/ 1/95.

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