The cell-adhesion molecule N-cadherin is critical for the tumour transition from a relatively benign to a very aggressive form of prostate cancer, reports an article published online this week in Nature Medicine. Therapeutic targeting of this adhesion molecule may have future clinical benefits for the treatment of prostate cancer.
Men with prostate cancer tend to respond to castration therapy, as prostate tumours are often dependent on androgenic hormones to grow. If, on the other hand, the tumour becomes androgen-independent and resistant to castration, the disease becomes lethal. What controls the transition to the castration-resistant state has been unknown.
Robert Reiter and his colleagues found that the expression of N-cadherin, a protein that acts as molecular glue between cells, is increased in tumours of people with castration-resistant prostate cancer. They found that forced expression of N-cadherin in androgen-dependent prostate cancer cells made them resistant to castration and promoted cancer metastasis. Monoclonal antibodies against N-cadherin reduced proliferation, adhesion and metastasis of prostate cancer cells transplanted into mice, leading in some cases to complete tumour regression.