Hyaluronan-CD44 promotes phospholipase C-mediated Ca2+ signaling and cisplatin resistance in head and neck cancer

Steven J. Wang, Lilly Y.W. Bourguignon

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Objective: To investigate whether hyaluronan (HA)-CD44 promotes head and neck squamous cell carcinoma (HNSCC) cisplatin resistance and whether HA-CD44 promotes phospholipase C (PLC)-mediated Ca2+ signaling to alter cisplatin sensitivity in HNSCC. Design: Cell line study. Main Outcome Measures: Tumor cell growth with the chemotherapeutic drug cisplatin was measured in the presence or absence of HA, anti-CD44 antibody plus HA, and other inhibitors of the PLC-mediated Ca2+ signaling pathway. Ca2+ mobilization was measured with fluorescence spectrophotometry using the Ca2+ binding dye Fura/2AM. Results: In the absence of HA, cisplatin inhibited tumor cell growth. The addition of HA, but not HA plus anti-CD44 antibody, resulted in a 5-fold reduced ability of cisplatin to cause HNSCC cell death, suggesting that HA can promote CD44-dependent cisplatin resistance. Fluorescence spectrophotometry demonstrated that HA can promote CD44-dependent Ca 2+ mobilization in HNSCC. On the other hand, the presence of U73122, a PLC inhibitor, and 2-aminoethoxydiphenyl borate, an inositol-1,4,5- triphosphate receptor inhibitor, eliminated HA-mediated Ca2+ mobilization and HA-mediated cisplatin resistance in these cell lines. Conclusions: Our results indicate that HA-CD44 signaling influences cisplatin sensitivity in HNSCC cell growth. In particular, HA-CD44 promotion of PLC-mediated Ca2+ signaling plays a role in cisplatin resistance in HNSCC cells. Perturbation of this HA-CD44-mediated signaling pathway may be a promising target to overcome cisplatin resistance in HNSCC.

Original languageEnglish (US)
Pages (from-to)19-24
Number of pages6
JournalArchives of Otolaryngology - Head and Neck Surgery
Volume132
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

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