Wen W N
Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei.
In Vitro Cell Dev Biol Anim. 2001 Nov-Dec;37(10):668-75. doi: 10.1290/1071-2690(2001)037<0668:MIASFI>2.0.CO;2.
NPC-N cells were normal human nasopharvngeal epithelial cells transformed by transfection with human papillomavirus type 16 deoxyribonucleic acid. Bovine pituitary extract (BPE) was one of the indispensable ingredients for in vitro culture of NPC-N cells in a serum-free medium. Chromatographic fractionation of BPE and subsequent immunoblotting analyses identified the hemoglobin growth-stimulating factor. Methemoglobin (metHb) was then synthesized, and also found to be growth stimulating. The growth-stimulating effect of metHb was abolished when NPC-N cells were cultured in a medium that also contained haptoglobin, a molecule that binds to hemoglobin. A defined medium consisting of insulin and metHb was then developed for optimal growth of NPC-N cells. MetHb kept under the conditions identical to those of cell culture released hemin which also enhanced the cell growth. Though all the degradation products of hemin are currently known to be physiologically significant. only ferric iron derived from metHb or hemin could stimulate the growth of NPC-N cells. Abnormal vasculature showing leaky walls and hemorrhage is a common feature of malignant tumors. Hemoglobin originating from extravasated red blood cells and subsequently oxidized to metHb because of the presence of activated inflammatory cells might contribute to the increased proliferation of cancerous cells.
NPC-N细胞是通过用人乳头瘤病毒16型脱氧核糖核酸转染而转化的正常人鼻咽上皮细胞。牛垂体提取物(BPE)是在无血清培养基中体外培养NPC-N细胞不可或缺的成分之一。对BPE进行色谱分离并随后进行免疫印迹分析鉴定出了血红蛋白生长刺激因子。然后合成了高铁血红蛋白(metHb),并且发现其也具有生长刺激作用。当NPC-N细胞在还含有与血红蛋白结合的分子触珠蛋白的培养基中培养时,metHb的生长刺激作用被消除。然后开发了一种由胰岛素和metHb组成的限定培养基,用于NPC-N细胞的最佳生长。在与细胞培养相同的条件下保存的metHb释放出血红素,这也增强了细胞生长。尽管目前已知血红素的所有降解产物都具有生理意义,但只有源自metHb或血红素的三价铁才能刺激NPC-N细胞的生长。显示壁渗漏和出血的异常脉管系统是恶性肿瘤的常见特征。源自外渗红细胞并随后由于活化炎症细胞的存在而氧化为metHb的血红蛋白可能有助于癌细胞增殖增加。