Gene expression profiles of rat tissues surrounding Vcap xenograft tumors with chemical or physical denervation.

We propose that nerves play a trophic function for epithelium, not only during development, but also in adult homeostasis. Hence, nerves are likely key in cancer progression. Furthermore nerves are a functional regulator of prostate cancer genesis and progression to malignancy. A further understanding of the role of nerves in prostate cancer progression and a dissection of specific mechanisms would aid in identifying potential therapeutic targets that are centered on cancer-nerve interactions. To address this in detail, we have examined the effects of nerve function in the VCaP prostate cancer xenograft model and have elucidated differential gene expression profiles in this model. Owing to the greater ease of surgical manipulation of the neural anatomy of rats, and the relative ease of maintenance of animals post-surgery, we choose a nude rat orthotopic VCaP model to test the functional significance of nerves in a human xenograft cancer model. For physical denervation we choose the major pelvic ganglia (MPG) excision, with particular care to avoid blood vessels since vessels and nerves are intimately connected and travel together in neurovascular bundles. For physical denervation we choose the major pelvic ganglia (MPG) excision, with particular care to avoid blood vessels. Sham surgery was used as control. In order to assess a comparative chemical denervation, we used Botulinum toxin (botox) and saline as a vehicle injection as control. To determine the effects of denervation on the non-neoplastic epithelium we laser captured the viable non neoplastic cancer epithelial cells, away from the tumors, in both the treated and control animals. We extracted RNA and performed gene array studies.