Format

Send to

Choose Destination
Arch Otolaryngol Head Neck Surg. 2006 Jan;132(1):19-24.

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

Author information

1
Department of Otolaryngology-Head and Neck Surgery and Endocrine Unit, Department of Medicine, University of California-San Francisco, 4150 Clement Street #112B, San Francisco, CA 94121, USA. swang@ohns.ucsf.edu

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 Ca2+ 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.

PMID:
16415424
DOI:
10.1001/archotol.132.1.19
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center