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Neutral endopeptidase 24.11 loss in metastatic human prostate cancer contributes to androgen-independent progression

Nature Medicine volume 4, pages 50–57 (1998)Cite this article

Abstract

Neutral endopeptidase 24.11 (NEP) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). We report that NEP expression and catalytic activity are lost in vitro in androgen-independent but not androgen-dependent PC cell lines. In vivo, NEP protein expression is commonly decreased in cancer cells of metastatic PC specimens from patients with androgen-independent but not androgen-dependent PC. Overexpression of NEP in androgen-independent PC cells or incubation with recombinant NEP inhibits PC cell growth. Furthermore, in androgen-dependent PC cells, expression of NEP is transcriptionally regulated by androgen and decreases with androgen withdrawal. These data suggest that decreased NEP expression, common in androgen-independent PCs, is facilitated by the elimination of androgens, and that NEP loss plays an important role in the development of androgen-independent PC by allowing PC cells to use mitogenic neuropeptides as an alternate source to androgen in order to stimulate cell proliferation.

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Authors and Affiliations

  1. Genitourinary Oncology Research Laboratory, Memorial Sloan-Kettering Cancer Center, S724, 1275 York Avenue, New York, New York, 10021, USA

    Christos N. Papandreou, Badar Usmani, Yiping Geng, Thomas Bogenrieder, Ronald Freeman & David M. Nanus

  2. Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, 1275 York Avenue, New York, New York, 10021, USA

    Christos N. Papandreou, Howard I. Scher & David M. Nanus

  3. Department of Pharmacology, Mount Sinai School of Medicine of the City University of New York, One Gustave L. Levy Place, New York, New York, 10029, USA

    Sherwin Wilk

  4. Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021, USA

    Connie L. Finstad

  5. Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021, USA

    Victor E. Reuter

  6. Urologic Oncology Research Laboratory, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021, USA

    C. Thomas Powell

  7. Hematopoietic Cancer Immunochemistry Laboratory, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021, USA

    David Scheinberg

  8. Arris Pharmaceutical, 180 Kimball Way, South San Francisco, California, 94080, USA

    Catherine Magill

  9. American Health Foundation, 1 Dana Road, Valhalla, New York, 10595, USA

    Anthony P. Albino

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Papandreou, C., Usmani, B., Geng, Y. et al. Neutral endopeptidase 24.11 loss in metastatic human prostate cancer contributes to androgen-independent progression. Nat Med 4, 50–57 (1998). https://doi.org/10.1038/nm0198-050

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