Sympathetic axonogenesis promotes adenoid cystic carcinoma progression Journal Article
| Authors: | Chen, C. H.; Reva, B.; Katabi, N.; Wizel, A.; Xu, H.; Ho, A. L.; Morris, L. G. T.; Bakst, R. L.; Parikh, A. S.; Drier, Y.; Deborde, S.; Wong, R. J. |
| Article Title: | Sympathetic axonogenesis promotes adenoid cystic carcinoma progression |
| Abstract: | Nerves are integral to the adenoid cystic carcinoma (ACC) microenvironment. The strong association of ACC with perineural invasion (PNI) is considered a hallmark of this disease. In human salivary ACC, we identify intratumoral, small-caliber, disorganized sympathetic nerves not observed in other salivary neoplasms. Norepinephrine or sympathetic ganglia explants enhance ACC proliferation in vitro. Two novel orthotopic ACC patient-derived xenograft (PDX) models recapitulate ACC morphology and demonstrate sympathetic innervation. Pharmacologic or surgical blockade of sympathetic nerves decreases ACC PDX growth. Bulk RNA sequencing of salivary ACC reveals correlations between noradrenergic nerve development signatures and worse patient survival. Metastatic ACC foci exhibit lower nerve signature gene expression levels than primary ACC. Sympathetic innervation in ACC is distinct from PNI and reflects tumor axonogenesis driven by noradrenergic neural development programs. These programs support ACC progression, are associated with poor prognosis, and may be inhibited as a therapeutic strategy. © 2025 Chen et al. |
| Keywords: | genetics; cell proliferation; mouse; animal; metabolism; animals; mice; pathology; cell line, tumor; disease progression; tumor cell line; salivary gland tumor; salivary gland neoplasms; adenoid cystic carcinoma; carcinoma, adenoid cystic; disease exacerbation; axons; ceftriaxone; noradrenalin; sympathetic nervous system; norepinephrine; adrenergic system; humans; human; female |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 222 |
| Issue: | 7 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2025-07-07 |
| Start Page: | e20242250 |
| Language: | English |
| DOI: | 10.1084/jem.20242250 |
| PUBMED: | 40272482 |
| PROVIDER: | scopus |
| PMCID: | PMC12020745 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding authors are Richard Wong and Sylvie Deborde -- Source: Scopus |
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