Brożyna Anna A, Jochymski Cezary, Janjetovic Zorica, Jóźwicki Wojciech, Tuckey Robert C, Slominski Andrzej T
Department of Tumor Pathology and Pathomorphology, the Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-796 Bygoszcz, Poland.
Department of Tumor Pathology and Pathomorphology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, 85-796 Bygoszcz, Poland.
Int J Mol Sci. 2014 Oct 20;15(10):19000-17. doi: 10.3390/ijms151019000.
The major role of 24-hydroxylase (CYP24A1) is to maintain 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) homeostasis. Recently, it has been discovered that CYP24A1 also catalyses the hydroxylation of 20(OH)D3, producing dihydroxy-derivatives that show very effective antitumorigenic activities. Previously we showed a negative correlation of vitamin D receptor (VDR) and CYP27B1 expression with progression, aggressiveness and overall or disease-free survivals of skin melanomas. Therefore, we analyzed CYP24A1 expression in relation to clinicopathomorphological features of nevi, skin melanomas and metastases. In melanocytic tumors, the level of CYP24A1 was higher than in the normal epidermis. The statistically highest mean CYP24A1 level was found in nevi and early stage melanomas. With melanoma progression, CYP24A1 levels decreased and in advanced stages were comparable to the normal epidermis and metastases. Furthermore, the CYP24A1 expression positively correlated with VDR and CYP27B1, and negatively correlated with mitotic activity. Lower CYP24A1 levels correlated with the presence of ulceration, necrosis, nodular type and amelanotic phenotypes. Moreover, a lack of detectable CYP24A1 expression was related to shorter overall and disease-free survival. In conclusion, the local vitamin D endocrine system affects melanoma behavior and an elevated level of CYP24A1 appears to have an important impact on the formation of melanocytic nevi and melanomagenesis, or progression, at early stages of tumor development.
24-羟化酶（CYP24A1）的主要作用是维持1,25-二羟基维生素D3（1,25(OH)2D3）的内稳态。最近，人们发现CYP24A1还催化20(OH)D3的羟化反应，生成具有非常有效的抗肿瘤活性的二羟基衍生物。此前我们发现维生素D受体（VDR）和CYP27B1的表达与皮肤黑色素瘤的进展、侵袭性以及总体或无病生存率呈负相关。因此，我们分析了CYP24A1的表达与痣、皮肤黑色素瘤和转移灶的临床病理形态学特征之间的关系。在黑素细胞肿瘤中，CYP24A1的水平高于正常表皮。在痣和早期黑色素瘤中发现CYP24A1的平均水平在统计学上最高。随着黑色素瘤的进展，CYP24A1水平下降，在晚期与正常表皮和转移灶相当。此外，CYP24A1的表达与VDR和CYP27B1呈正相关，与有丝分裂活性呈负相关。较低的CYP24A1水平与溃疡、坏死、结节型和无色素表型的存在相关。此外，检测不到CYP24A1表达与较短的总体生存期和无病生存期相关。总之，局部维生素D内分泌系统影响黑色素瘤的行为，CYP24A1水平升高似乎对黑素细胞痣的形成以及肿瘤发生早期的黑色素瘤发生、进展具有重要影响。
