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

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.