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B-cell-derived lymphotoxin promotes castration-resistant prostate cancer

Author

Listed:
  • Massimo Ammirante

    (Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA)

  • Jun-Li Luo

    (Scripps Research Institute-Florida, 130 Scripps Way, Jupiter, Florida 33458, USA)

  • Sergei Grivennikov

    (Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA)

  • Sergei Nedospasov

    (Laboratory of Molecular Immunology, Engelhardt Institute of Molecular Biology, 119991, Moscow, Russia)

  • Michael Karin

    (Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA)

Abstract

Lymphotoxin's role in prostate cancer progression In the early stages of prostate cancer, cancerous cell growth is dependent on androgens, hence the success of prostatectomy, radiation and androgen-ablating drug therapies. With time, the cancer often develops into an androgen-insensitive, therapy-resistant form with high mortality rates. Work in mouse models of prostate cancer raises the possibility that androgen-ablating therapies may indirectly promote the development of metastatic secondary tumours. Ammirante et al. report that in mice with transgene-induced spontaneous prostate cancer, B-cell infiltration, a component of the natural inflammatory response, activates lymphotoxin release, which stimulates metastasis. In the second model, involving subcutaneous transplantation of an androgen-dependent prostate cancer cell line, it is shown that regression of androgen-deprived primary tumours results in an inflammatory response — and lymphotoxin production. Interfering with the lymphotoxin pathway may therefore offer therapeutic strategies for androgen-independent prostate cancer.

Suggested Citation

  • Massimo Ammirante & Jun-Li Luo & Sergei Grivennikov & Sergei Nedospasov & Michael Karin, 2010. "B-cell-derived lymphotoxin promotes castration-resistant prostate cancer," Nature, Nature, vol. 464(7286), pages 302-305, March.
    • Handle: RePEc:nat:nature:v:464:y:2010:i:7286:d:10.1038_nature08782
    DOI: 10.1038/nature08782
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