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

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...

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Published in:Nature communications 2015-04, Vol.6 (1), p.6885-6885, Article 6885
Main Authors: Scanlon, Christina Springstead, Banerjee, Rajat, Inglehart, Ronald C., Liu, Min, Russo, Nickole, Hariharan, Amirtha, van Tubergen, Elizabeth A., Corson, Sara L., Asangani, Irfan A., Mistretta, Charlotte M., Chinnaiyan, Arul M., D’Silva, Nisha J.
Format: Article
Language:English
Subjects:
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Animals
Cell Line, Tumor
Chick Embryo
Cyclooxygenase 2 - metabolism
Disease Progression
Galanin - metabolism
Head and Neck Neoplasms - metabolism
Humanities and Social Sciences
Humans
Mice
multidisciplinary
Neoplasm Invasiveness
Neurites - metabolism
NFATC Transcription Factors - metabolism
Random Allocation
Rats
Receptor, Galanin, Type 2 - metabolism
Science
Science (multidisciplinary)
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Summary: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. Perineural invasion occurs in many head and neck cancers and is thought to be an active process where tumour cells degrade the neural sheath. Here the authors show that the neuropeptide galanin mediates the crosstalk between nerves and cancer cells to promote malignant progression.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms7885