SQUAMOUS CARCINOMA CELL-LINES PRODUCE 1,25 DIHYDROXYVITAMIN-D, BUT FAIL TO RESPOND TO ITS PRODIFFERENTIATING EFFECT
SQUAMOUS CARCINOMA CELL-LINES PRODUCE 1,25 DIHYDROXYVITAMIN-D, BUT FAIL TO RESPOND TO ITS PRODIFFERENTIATING EFFECT
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DOI：
10.1111/1523-1747.ep12481267
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发表时间：
1991-09-01
影响因子：
6.5
通讯作者：
GEE, E
中科院分区：
文献类型：
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作者：
BIKLE, DD;PILLAI, S;GEE, E
维生素D3的活性代谢物1,25二羟基维生素D3 [1,25(OH)2D]由正常人角质形成细胞（NKC）产生并调节其分化。鳞状癌细胞（SCC）系缺乏体外分化的能力，这可能涉及有缺陷的1,25(OH)2D合成或反应。为了确定这种可能性，我们获得了4个SCC系（12F2、12B2、25和A431），并首先确定它们是否能从底物25羟基维生素D3 （250HD）中产生1,25(OH)2D。所有可能（12F2 > NKC > 25 > 12B2 > A431）。此外，外源添加1,25(OH)2D抑制了所有细胞系中1,25(OH)2D的产生，并刺激了24,25二羟基维生素D3 [24,25(OH)2D]的产生，但效力不同（25 = A431 > NKC > 12B2 > 12F2）。细胞结合研究表明，12F2和12B2中没有发现NKC中1,25(OH)2D的高亲和力结合位点。当确定1,25(OH)2D对分化的影响时，尽管一些细胞系对1,25(OH)2D的增殖[在低1,25(OH)2D浓度下]或抗增殖[在高1,25(OH)2D浓度下]有反应，但只有NKC对角化包膜形成的增加有反应。因此，尽管SCC细胞系合成1,25(OH)2D，并对外源性1,25(OH)2D做出响应，适当调节内源性250HD代谢，但这些细胞系对这种维生素D代谢物的分化影响没有反应。
The active metabolite of vitamin D3, 1,25 dihydroxyvitamin D3 [1,25(OH)2D], is produced by normal human keratinocytes (NKC) and regulates their differentiation. Squamous carcinoma cell (SCC) lines lack the ability to differentiate in vitro, which might involve defective 1,25(OH)2D synthesis or response. To address this possibility we obtained four SCC lines (12F2, 12B2, 25, and A431) and first determined whether they could produce 1,25(OH)2D from its substrate 25 hydroxyvitamin D3 (250HD). All could (12F2 > NKC > 25 > 12B2 > A431). Furthermore, exogenously added 1,25(OH)2D inhibited 1,25(OH)2D production and stimulated 24,25 dihydroxyvitamin D3 [24,25(OH)2D] production in all cell lines but with different potency (25 = A431 > NKC > 12B2 > 12F2). Cellular binding studies suggested that the high-affinity binding site for 1,25(OH)2D in NKC is not found in 12F2 and 12B2. When the effect of 1,25(OH)2D on differentiation was determined, only NKC responded with an increase in cornified envelope formation, although some of the cell lines responded to the proliferative [at low 1,25(OH)2D concentration] or antiproliferative [at high 1,25(OH)2D concentration] effect of 1,25(OH)2D. Thus, although SCC lines synthesize 1,25(OH)2D and respond to exogenous 1,25(OH)2D with respect to appropriate regulation of endogenous 250HD metabolism, these cell lines fail to respond to the differentiating influence of this vitamin D metabolite.