Interim progress report

HYALURONAN Signaling in Head and Neck Cancer Progression

2005 AHNS Young Investigator Award

Steven J. Wang, MD Principal Investigator

Award period: 2005-2007. Published November 28, 2006

PROGRESS: 

Through the support of the AHNS/AAO-HNSF Young Investigator Award, I was able to carry out studies examining the role of hyaluronan (HA) signaling in head and neck cancer progression and chemotherapy resistance.  My work has demonstrated that HA-CD44 interactions promote both phospholipase C- and epidermal growth factor receptor (EGFR)-mediated signaling pathways, resulting in multiple tumor progression behaviors and chemotherapy resistance in head and neck cancer cell lines.  One of the downstream signaling targets influenced by HA-CD44 promotion of phospholipase C is topoisomerase II, which is a well-known regulator of DNA function and metabolism.  Studies of CD44 variant isoforms in head and neck cancer cell lines determined that expression of CD44 v3 containing isoforms are associated with tumor progression.  During the past 15 months, research supported by this grant has resulted in 4 abstract presentations and 4 peer-reviewed manuscripts.  In addition, I successfully applied and obtained a VA Career Development Award, starting in 2007, which will allow me to continue along my current research focus.

ABSTRACTS AND MANUSCRIPTS: 

• Hyaluronan-CD44 signaling promotes chemotherapy resistance in head and neck cancer.  Annual Meeting of the American Academy of Otolaryngology—Head and Neck Surgery Foundation, Los Angeles, CA, September 25-28, 2005.
• Hyaluronan promotes CD44-epidermal growth factor interaction, oncogenic signaling, and chemotherapy resistance in head and neck cancer.  Annual Meeting of the American Association for Cancer Research, Washington, D.C., April 3, 2006.
• Hyaluronan-CD44 interaction influences topoisomerase II activity and etoposide cytotoxicity in head and neck cancer.  Annual Meeting of the American Head and Neck Society and Research Workshop on the Biology, Prevention and Treatment of Head and Neck Cancer, Chicago, IL,  August 18, 2006.
• The Association of CD44 v3 isoforms with head and neck squamous cell carcinoma progression.  Annual Meeting of the American Academy of Otolaryngology—Head and Neck Surgery Foundation, Toronto, ON, September 16-20, 2006.

• Wang SJ, Bourguignon LY. Hyaluronan-CD44 promotes phospholipase C-mediated Ca2+ signaling and cisplatin resistance in head and neck cancer.  Arch Otolaryngol Head Neck Surg 2006;132:19-24.
• Wang SJ, Bourguignon LY.  Hyaluronan and the interaction between CD44 and epidermal growth factor receptor in oncogenic signaling and chemotherapy resistance in head and neck cancer.  Arch Otolaryngol Head Neck Surg  2006;132:771-778.
• Wang SJ, Wreesmann VB, Bourguignon LY.  Association of CD44 v3 containing isoforms in tumor cell growth, migration, matrix metalloproteinase expression, and lymph node metastasis in head and neck cancer.  Head Neck (in press).
• Wang SJ, Peyrollier K, Bourguignon LY.  Hyaluronan-CD44 interaction influences topoisomerase II activity and etoposide cytotoxicity in head and neck cancer.  Arch Otolaryngol Head Neck Surg (in press).

Expenditures for the first Year:  Expenditures for the first year included disposable laboratory reagents such as antibodies and cell culture supplies, statistical analysis support, and multimedia work for abstract and manuscript presentation.

Budget and Plans for the Second Year:  Budget and plans for second year include continuing to carry out cell culture experiments to characterize the interaction of HA-CD44 with EGFR and phospholipase C signaling pathways to promote head and neck cancer progression and treatment resistance.