Open Access Highly Accessed Research article

Inverse expression of hyaluronidase 2 and hyaluronan synthases 1–3 is associated with reduced hyaluronan content in malignant cutaneous melanoma

Siiskonen Hanna1*, Poukka Mari1, Tyynelä-Korhonen Kristiina2, Sironen Reijo345 and Pasonen-Seppänen Sanna1

Author Affiliations

1 Institute of Biomedicine/Anatomy, University of Eastern Finland, P.O.B. 1627, Kuopio, FIN-70211, Finland

2 Cancer Center, Kuopio University Hospital, Kuopio, Finland

3 Institute of Clinical Medicine/Clinical Pathology, University of Eastern Finland, Kuopio, Finland

4 Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland

5 Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland

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BMC Cancer 2013, 13:181  doi:10.1186/1471-2407-13-181

Published: 5 April 2013



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.


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.


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.


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.

Hyaluronan; Hyaluronan synthase; Hyaluronidase; Cutaneous tumor; Benign nevus; Melanoma