Clusterin (CLU) and Melanoma Growth: CLU is Expressed in Malignant Melanoma and 1,25-Dihydroxyvitamin D₃ Modulates Expression of CLU in Melanoma Cell Lines In Vitro

Abstract

Background: The glycoprotein clusterin (CLU) has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, while a secretory form (sCLU) is pro-survival. CLU expression has been associated with tumorigenesis and the progression of various malignancies. Materials and Methods: The expression of CLU was studied immunohistochemically in paraffin sections of primary cutaneous malignant melanomas, metastases of malignant melanomas and acquired melanocytic naevi. Using PCR and Western blotting, the expression of CLU was also investigated in various vitamin D-responsive (MeWo, SK-MEL-28) and vitamin D-resistant melanoma cell lines (SK-MEL-5, SK-MEL-25), as well as in normal human melanocytes (NHM), along with 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] treatment. Results: In contrast to acquired melanocytic naevi, CLU immunoreactivity was found in primary cutaneous malignant melanomas and metastases of malignant melanomas in situ. Both CLU protein and RNA were detected in melanoma cell lines and NHM. Treatment with 1,25(OH)₂D₃ modulated CLU's expression in vitamin D-responsive but not in -resistant melanoma cell lines. Conclusion: CLU may be of importance for the progression of malignant melanoma. The growth regulatory effects of 1,25(OH)₂D₃ in melanoma cell lines may, at least in part, be mediated via modulation of CLU expression.