Journal
LARYNGOSCOPE
Volume 126, Issue 5, Pages E184-E190Publisher
WILEY-BLACKWELL
DOI: 10.1002/lary.25808
Keywords
Larynx cancer; cancer stem cells; targeted therapy; CD44; hyaluronan nanoconjugate
Funding
- AHNS Alando J. Ballantyne Research Grant
- University of Michigan Department of Surgery
- University of Michigan Cancer Center Support Grant
- National Cancer Institute [R01CA173292]
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Objectives/HypothesisTo evaluate the efficacy of peritumoral hyaluronic acid (HA)-cisplatin therapy in a murine model of laryngeal squamous cell carcinoma and to evaluate its effect on cancer stem cells (CSCs). Study DesignAn orthotopic murine study utilizing University of Michigan squamous cell carcinoma-12 (UMSCC-12) laryngeal cancer cells was conducted in randomized controlled fashion with three treatment arms: saline, systemic cisplatin, and peritumoral HA-cisplatin. MethodsUMSCC-12 laryngeal cancer cells were inoculated into the buccal mucosa of athymic nude mice followed by weekly treatment with saline, systemic cisplatin, or peritumoral HA-cisplatin for 3 weeks. Tumor response and animal weight was monitored and change in CD44 proportion was analyzed ex vivo. ResultsHA-cisplatin demonstrated superior antitumor efficacy and greater reduction in CD44 positivity on ex vivo analysis. ConclusionsPeritumoral nanoconjugated HA-cisplatin provides superior antitumor efficacy compared to standard cisplatin therapy in an in vivo laryngeal cancer model. There was also selective targeting of CD44+ cancer cells with HA-cisplatin. This therapeutic strategy could represent the first selective laryngeal CSC-targeted therapy. Further preclinical investigation is warranted to evaluate its role for locally advanced head and neck cancer treatment. Level of EvidenceNA Laryngoscope, 126:E184-E190, 2016
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