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

Priscila O de Lima; Natasa Broit; Johnson D Huang; Jae H Lim; Damien J Gardiner; Ian S Brown; Benedict J Panizza; Glen M Boyle; Fiona Simpson

doi:10.3389/fonc.2023.1231104

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

Front Oncol. 2023 Sep 7:13:1231104. doi: 10.3389/fonc.2023.1231104. eCollection 2023.

Authors

Priscila O de Lima¹, Natasa Broit², Johnson D Huang¹, Jae H Lim^{2

3}, Damien J Gardiner^{2

3}, Ian S Brown^{4

5}, Benedict J Panizza^{3

6}, Glen M Boyle^{2

7}, Fiona Simpson¹

Affiliations

¹ Frazer Institute, University of Queensland, Brisbane, QLD, Australia.
² Cancer Drug Mechanisms Group, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, QLD, Australia.
³ Queensland Skull Base Unit and Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, QLD, Australia.
⁴ Envoi Pathology, Brisbane, QLD, Australia.
⁵ Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
⁶ Department of Otolaryngology-Head and Neck Surgery, Kaiser Moanalua Medical Center, Honolulu, HI, United States.
⁷ Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.

Abstract

Introduction: Cutaneous 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.

Methods: A431 cells were injected into the whisker pads of BALB/c Foxn1^nu 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.

Results: The 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.

Discussion: This 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.

Keywords: LOXL2; cutaneous SCC of the head and neck; in vivo mouse models; perineural invasion; perineural spread.

Grants and funding

This work was supported by the Queensland Head and Neck Cancer Centre Grant to Boyle. UQ International scholarship and post-doctoral fellowship to PL. FS acknowledges funding from the National Health and Medical Research Council Ideas Grant APP2001396 and Philanthropic funding from Merchant Charitable Foundation (Grant number: 2019002447), Princess Alexandra Hospital Research Fund (Grant number: 2019002447) and Aveo communities.