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

BMC Cancer

Siiskonen Hanna¹  Poukka Mari¹  Tyynelä-Korhonen Kristiina²  Sironen Reijo³  Pasonen-Seppänen Sanna¹ 

[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] Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland

关键词: Melanoma;    Benign nevus;    Cutaneous tumor;    Hyaluronidase;    Hyaluronan synthase;    Hyaluronan;   

Others  :  1079809
DOI  :  10.1186/1471-2407-13-181

 received in 2012-11-20, accepted in 2013-04-02,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Hanna et al.; licensee BioMed Central Ltd.

【 图 表 】

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