The effect of 1,25-dihydroxyvitamin D3 on lymphoma cell lines and expression of vitamin D receptor in lymphoma.
1,25(OH)2D3 promotes differentiation and has an antiproliferative effect in a variety of cell lines derived from the immunohaematopoetic system. alpha-Calcidol which is metabolised to 1,25(OH)2D3 has been shown to produce tumour regression in follicular low grade non-Hodgkin's lymphoma (NHL) and the dose limiting toxicity is hypercalcaemia. The cellular action of 1,25(OH)2D3 is mediated by binding to an intracellular protein, the vitamin D receptor (VDR). We have evaluated the activity of 1,25(OH)2D3 and its non-calcaemogenic analogue MC903 in the SU-DHL4 and SU-DUL5 B cell lines which carry the 14;18 translocation characteristic of follicular NHL, and also the expression of the VDR in a range of B cell NHLs. Both agents induced differentiation and had an antiproliferative effect on the SU-DHL4 and SU-DUL5 cell lines. However this occurred at a relatively high concentration (10(-7) M) which exceeds the physiological concentration of 1,25(OH)2D3 by approximately 10(3)-10(4)-fold. Expression of the VDR was low in each cell line and in the low grade lymphoma tumour samples. To account for the observed clinical response to 1 alpha OHD3 (alpha-calcidol) in follicular NHL a network is suggested whereby 1,25(OH)2D3 modulates the activity of CD4+T cells which have previously been shown to promote follicle centre cell proliferation. Vitamin D3 analogues may enable serum levels to be achieved which produce a direct action on follicular lymphoma cells without disturbing calcium metabolism.
Lymphoma Unit, Royal Marsden Hospital, Sutton, Surrey, UK.
T
T
Hickish
D
D
Cunningham
K
K
Colston
B C
BC
Millar
J
J
Sandle
A G
AG
Mackay
M
M
Soukop
J
J
Sloane
D001706:Biopsy; D002117:Calcitriol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018167:Receptors, Calcitriol; C055085:calcipotriene; D002117:Calcitriol