Science · 2013 · 1.2K citations · 30 references
MedicineCancer BiologyOncologyMetastasisNeuro-oncologyTumor MicroenvironmentAngiogenesisAngiogenesis In CancerMetastatic DisseminationNervous TissueProstate CancerProstate PhysiologyAfferent Nerve FibersAngiogenesis In Tumor PromotionAngiogenesis-driven GrowthAutonomic Nervous System EffectsMicroenvironmental InteractionsTumor DisseminationTumor Microenvironment ResponsivenessTumor Neovascularization
Solid tumors remodel their microenvironment, exemplified by angiogenesis, and recent work shows that developing autonomic nerve fibers also promote prostate cancer growth and metastasis. In prostate cancer models, ablating sympathetic nerves halted early tumor growth while inhibiting parasympathetic nerves reduced dissemination, and human samples with dense nerve fibers correlated with poorer outcomes, suggesting autonomic‑targeting drugs could be therapeutic.
Cancer Hits a Nerve Solid tumors sculpt their microenvironment to maximize their growth and metastatic potential. This concept is illustrated most famously by tumor angiogenesis, a process whereby tumors induce the growth of new blood vessels to boost their supply of oxygen and blood-borne nutrients. Magnon et al. (p. 10.1126/science.1236361 ; see the Perspective by Isaacs ) now highlight the important contribution made by another microenvironmental component—developing autonomic nerve fibers—to tumor growth and metastasis. In mouse models of prostate cancer, surgical or chemical destruction of sympathetic nerves prevented early-stage growth of tumors, whereas pharmacological inhibition of parasympathetic nerves inhibited tumor dissemination. In a small study of human prostate cancer specimens, the presence of a high density of nerve fibers in and around the tumor tissue was found to correlate with poor clinical outcome. These results raise the possibility that drugs targeting the autonomic nervous system may have therapeutic potential for prostate cancer.
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