Tumor-associated genetic amplifications impact extracellular vesicle miRNA cargo and their recruitment of nerves in head and neck cancer.

Autor: Restaino AC; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, South Dakota, USA., Walz A; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, South Dakota, USA., Barclay SM; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, South Dakota, USA., Fettig RR; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, South Dakota, USA., Vermeer PD; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, South Dakota, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Jul 15; Vol. 38 (13), pp. e23803.
DOI: 10.1096/fj.202400625RR
Abstrakt: Cancer neuroscience is an emerging field of cancer biology focused on defining the interactions and relationships between the nervous system, developing malignancies, and their environments. Our previous work demonstrates that small extracellular vesicles (sEVs) released by head and neck squamous cell carcinomas (HNSCCs) recruit loco-regional nerves to the tumor. sEVs contain a diverse collection of biological cargo, including microRNAs (miRNAs). Here, we asked whether two genes commonly amplified in HNSCC, CCND1, and PIK3CA, impact the sEV miRNA cargo and, subsequently, sEV-mediated tumor innervation. To test this, we individually overexpressed these genes in a syngeneic murine HNSCC cell line, purified their sEVs, and tested their neurite outgrowth activity on dorsal root ganglia (DRG) neurons in vitro. sEVs purified from Ccnd1-overexpressing cells significantly increased neurite outgrowth of DRG compared to sEVs from parental or Pik3ca over-expressing cells. When implanted into C57BL/6 mice, Ccnd1 over-expressing tumor cells promoted significantly more tumor innervation in vivo. qPCR analysis of sEVs shows that increased expression of Ccnd1 altered the packaging of miRNAs (miR-15-5p, miR-17-5p, and miR-21-5p), many of which target transcripts important in regulating axonogenesis. These data indicate that genetic amplifications harbored by malignancies impose changes in sEV miRNA cargo, which can influence tumorc innervation.
(© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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