Effects of peritumoral nanoconjugated cisplatin on laryngeal cancer stem cells

Laryngoscope. 2016 May;126(5):E184-90. doi: 10.1002/lary.25808. Epub 2015 Dec 21.

Abstract

Objectives/hypothesis: To 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 design: An 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.

Methods: UMSCC-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.

Results: HA-cisplatin demonstrated superior antitumor efficacy and greater reduction in CD44 positivity on ex vivo analysis.

Conclusions: Peritumoral 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 evidence: NA Laryngoscope, 126:E184-E190, 2016.

Keywords: CD44; Larynx cancer; cancer stem cells; hyaluronan nanoconjugate; targeted therapy.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Cisplatin / pharmacology*
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • Hyaluronan Receptors / drug effects
  • Hyaluronic Acid / pharmacology
  • Laryngeal Neoplasms / drug therapy*
  • Mice
  • Mice, Nude
  • Nanoconjugates / administration & dosage
  • Neoplastic Stem Cells / drug effects*
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Cd44 protein, mouse
  • Hyaluronan Receptors
  • Nanoconjugates
  • Hyaluronic Acid
  • Cisplatin