title: Role of hyaluronan synthase 2 to promote CD44-dependent oral cavity squamous cell carcinoma progression.
abstract: BACKGROUND
  CD44 is a transmembrane receptor found on many different benign and malignant cells. Hyaluronan (HA), a major component of the extracellular matrix, is the primary ligand for CD44 receptors. In cancer cells, HA interaction with CD44 promotes multiple signaling pathways that influence tumor cell progression behaviors in a variety of solid tumors. Increasing evidence indicates that HA and CD44 signaling play an important role in oral cavity squamous cell carcinoma progression. HA is primarily synthesized by hyaluronan synthases, and the current study investigated the role of hyaluronan synthase 2 (HAS 2) in oral cavity carcinoma progression behaviors.
  
  
  METHODS
  Analysis of HAS 2 mRNA and protein expression, HA production, and HAS 2-mediated tumor cell proliferation and migration behaviors with and without HAS 2 suppression were carried out on 2 established oral cavity cancer cell lines. Immunohistochemical analysis of HAS 2 and CD44 expression in oral cavity carcinoma tumor specimens was performed.
  
  
  RESULTS
  HAS 2 was expressed in the 2 oral cancer cell lines, HSC-3 and SCC-4. Suppression of HAS 2 expression resulted in CD44-dependent decreased tumor cell migration, decreased tumor cell growth, and increased cisplatin sensitivity, suggesting the importance of tumor cell HA production to promote in vitro tumor progression behaviors in oral cancer cells. Increased HAS 2 expression in oral cavity carcinoma clinical specimens was associated with poor clinicopathologic characteristics and worse disease-free survival.
  
  
  CONCLUSIONS
  HAS 2 may be a potential therapeutic target for the treatment of oral cavity cancer.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, Veterans Affairs Medical Center, San Francisco, California, USA. swang@ohns.ucsf.edu
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Wang
authors.forename: Christine
authors.initials: C
authors.lastname: Earle
authors.forename: Gabriel
authors.initials: G
authors.lastname: Wong
authors.forename: Lilly Y W
authors.initials: LY
authors.lastname: Bourguignon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D000076002:Hyaluronan Synthases; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D018960:Hyaluronan Receptors; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases