title: Inverse expression of hyaluronidase 2 and hyaluronan synthases 1-3 is associated with reduced hyaluronan content in malignant cutaneous melanoma.
abstract: BACKGROUND
  Hyaluronan is an extracellular matrix glycosaminoglycan involved in invasion, proliferation and metastasis of various types of carcinomas. In many cancers, aberrant hyaluronan expression implicates disease progression and metastatic potential. Melanoma is an aggressive skin cancer. The role of hyaluronan in melanoma progression including benign nevi and lymph node metastases has not been investigated earlier, nor the details of its synthesis and degradation.
  
  
  METHODS
  The melanocytic and dysplastic nevi, in situ melanomas, superficially and deeply invasive melanomas and their lymph node metastases were analysed immunohistochemically for the amount of hyaluronan, its cell surface receptor CD44, hyaluronan synthases 1-3 and hyaluronidases 1-2.
  
  
  RESULTS
  Hyaluronan content of tumoral cells in deeply invasive melanomas and metastatic lesions was clearly reduced compared to superficial melanomas or benign lesions. Furthermore, hyaluronan content in the stromal cells of benign nevi was higher than in the premalignant or malignant tumors. The immunopositivity of hyaluronidase 2 was significantly increased in the premalignant and malignant lesions indicating its specific role in the degradation of hyaluronan during tumor progression. Similarly, the expression of hyaluronan synthases 1-2 and CD44 receptor was decreased in the metastases compared to the primary melanomas.
  
  
  CONCLUSIONS
  These findings suggest that the reciprocal relationship between the degrading and synthesizing enzymes account for the alterations in hyaluronan content during the growth of melanoma. These results provide new information about hyaluronan metabolism in benign, premalignant and malignant melanocytic tumors of the skin.
authors.affiliation: Institute of Biomedicine/Anatomy, University of Eastern Finland, P.O.B. 1627, FIN-70211, Kuopio, Finland. hanna.siiskonen@uef.fi
authors.forename: Hanna
authors.initials: H
authors.lastname: Siiskonen
authors.forename: Mari
authors.initials: M
authors.lastname: Poukka
authors.forename: Kristiina
authors.initials: K
authors.lastname: Tyynelä-Korhonen
authors.forename: Reijo
authors.initials: R
authors.lastname: Sironen
authors.forename: Sanna
authors.initials: S
authors.lastname: Pasonen-Seppänen
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; C473096:Hyal2 protein, human; D006821:Hyaluronoglucosaminidase
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