Abstract 5221: Snail promotes neurite outgrowth in prostate cancer cells

Abstract

Abstract Neurite Outgrowth is a process where developing neurons produce new tentacle-like extensions as they grow in response to guidance cues. The projection can be an axon or a dendrite (nerve fibers). Nerve growth factors, or neurotrophins which are important for survival or growth, are one family of such stimuli that regulate neurite growth. Studies have also proposed that cancer cells stimulate their own innervations. Therefore, the concept of neoneurogenesis includes the development of nerve endings (axons)towards the tumor. Cancer cells are able to secrete neurite outgrowth-promoting molecules and axon guidance molecules that would stimulate and initiate the growth of these new axons to particular areas of the tumor. Neurite outgrowth involves reciprocal signaling interactions between tumor cells and nerves where invading tumor cells have acquired the ability to respond to pro-invasive signals within the peripheral nerve environment. Neurite Outgrowth could serve as a possible mechanism leading to invasion of cancer cells into the nerve sheath and subsequent metastasis. Snail1 or Snail is a zinc-finger protein that can down-regulate cell adhesion proteins such as E-cadherin by binding several E-boxes located in the promotor region, thereby inducing the epithelial mesenchymal transition (EMT) process to promote tumor migration and metastasis. Snail has also been shown to promote neuroendocrine differentiation. The hypothesis is that Snail can promote neurite outgrowth. For this study we utilized various prostate cancer cell lines: C42 NS, E006AA-hT (controls); C42 Snail shRNA, E006AA-hT (stable Snail knockdowns); LNCAP Neo (empty vector control) and LNCAP Snail (stably over-expressing Snail). Conditioned media collected from these cells was cultured with nerve cells (NS20Y) for 48 hours followed by a quantitative neurite outgrowth assay. Nerve growth factor (NGF) was utilized as a positive control. We also included Lanreotide, an inhibitor of neuroendocrine differentiation. After 48 hours, the nerve cells were incubated with Fix/Stain solution containing Cell Viability, and Cell Membrane stain, and nerve extensions quantified by analysis with a plate reader. Our results showed that C42 NS and E006AA-hT NS (Snail-high) conditioned media led to a higher neurite outgrowth compared to the Snail knocked down cells. We also observed that neurite outgrowth was blocked by Lanreotide inhibitor. In conclusion, Snail promotes neurite outgrowth via secretion of soluble factors, which can be inhibited by Lanreotide, a drug currently being used to treat patients with neuroendocrine tumors. Therefore, targeting cancer cell interaction with nerve cells may be helpful in halting prostate cancer progression/metastasis. GRANT SUPPORT: NIH 1P20MD002285, NIH/NCRR/RCMI G12RR003062-22 and NIH/NIGMS/RISE 5R25GM060414 Citation Format: Gabrielle J. Edwards. Snail promotes neurite outgrowth in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5221.