Galanin modulates the neural niche to favour perineural invasion in head and neck cancer

Christina Springstead Scanlon, Rajat Banerjee, Ronald C. Inglehart, Min Liu, Nickole Russo, Amirtha Hariharan, Elizabeth A. van Tubergen, Sara L. Corson, Irfan A. Asangani, Charlotte M. Mistretta, Arul M. Chinnaiyan and Nisha J. D’Silva ()
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Christina Springstead Scanlon: University of Michigan School of Dentistry
Rajat Banerjee: University of Michigan School of Dentistry
Ronald C. Inglehart: University of Michigan School of Dentistry
Min Liu: University of Michigan School of Dentistry
Nickole Russo: University of Michigan School of Dentistry
Amirtha Hariharan: University of Michigan School of Dentistry
Elizabeth A. van Tubergen: University of Michigan School of Dentistry
Sara L. Corson: University of Michigan School of Dentistry
Irfan A. Asangani: University of Michigan Medical School
Charlotte M. Mistretta: University of Michigan School of Dentistry
Arul M. Chinnaiyan: University of Michigan Medical School
Nisha J. D’Silva: University of Michigan School of Dentistry

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract Perineural invasion (PNI) is an indicator of poor survival in multiple cancers. Unfortunately, there is no targeted treatment for PNI since the molecular mechanisms are largely unknown. PNI is an active process, suggesting that cancer cells communicate with nerves. However, nerve–tumour crosstalk is understudied due to the lack of in vivo models to investigate the mechanisms. Here we developed an in vivo model of PNI to characterize this interaction. We show that the neuropeptide galanin (GAL) initiates nerve–tumour crosstalk via activation of its G protein-coupled receptor, GALR2. Our data reveal a novel mechanism by which GAL from nerves stimulates GALR2 on cancer cells to induce NFATC2-mediated transcription of cyclooxygenase-2 and GAL. Prostaglandin E2 promotes cancer invasion, and in a feedback mechanism, GAL released by cancer induces neuritogenesis, facilitating PNI. This study describes a novel in vivo model for PNI and reveals the dynamic interaction between nerve and cancer.

Date: 2015
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DOI: 10.1038/ncomms7885

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