Development of an in vivo murine model of perineural invasion and spread of cutaneous squamous cell carcinoma of the head and neck

Frontiers in Oncology

Oncology

Natasa Broit¹  Glen M. Boyle²  Damien J. Gardiner³  Jae H. Lim³  Ian S. Brown⁴  Priscila O. de Lima⁵  Fiona Simpson⁵  Johnson D. Huang⁵  Benedict J. Panizza⁶ 

[1] Cancer Drug Mechanisms Group, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, QLD, Australia;Cancer Drug Mechanisms Group, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, QLD, Australia;Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia;Cancer Drug Mechanisms Group, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, QLD, Australia;Queensland Skull Base Unit and Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, QLD, Australia;Envoi Pathology, Brisbane, QLD, Australia;Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia;Frazer Institute, University of Queensland, Brisbane, QLD, Australia;Queensland Skull Base Unit and Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, QLD, Australia;Department of Otolaryngology-Head and Neck Surgery, Kaiser Moanalua Medical Center, Honolulu, HI, United States;

关键词: perineural invasion;    perineural spread;    cutaneous SCC of the head and neck;    in vivo;    LOXL2;   

DOI  :  10.3389/fonc.2023.1231104

 received in 2023-05-30, accepted in 2023-07-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionCutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process is called perineural invasion (PNI) and spread (PNS). An in vivo sciatic nerve mouse model is used for cSCCHN PNI/PNS. Here we describe a complementary whisker pad model which allows for molecular studies investigating drivers of PNI/PNS in the head and neck environment.MethodsA431 cells were injected into the whisker pads of BALB/c Foxn1nu and NSG-A2 mice. Tumor progression was monitored by bioluminescence imaging and primary tumor resection was performed. PNI was detected by H&E and IHC. Tumor growth and PNI were assessed with inducible ablation of LOXL2.ResultsThe rate of PNI development in mice was 10%-28.6%. Tumors exhibited PNI/PNS reminiscent of the morphology seen in the human disease. Our model’s utility was demonstrated with inducible ablation of LOXL2 reducing primary tumor growth and PNI.DiscussionThis model consists in a feasible way to test molecular characteristics and potential therapies, offers to close a gap in the described in vivo methods for PNI/PNS of cSCCHN and has uses in concert with the established sciatic nerve model.

【 授权许可】

Unknown   
Copyright © 2023 de Lima, Broit, Huang, Lim, Gardiner, Brown, Panizza, Boyle and Simpson