Cancer cells uptake porphyrins via heme carrier protein 1
Cancer cells uptake porphyrins via heme carrier protein 1
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DOI：
10.1142/s1088424612501192
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发表时间：
2013-01-01
影响因子：
1.5
通讯作者：
Tamai, Ikumi
中科院分区：
文献类型：
--
作者：
Hiyama, Kazuhiro;Matsui, Hirofumi;Tamai, Ikumi
虽然外源性卟啉在癌细胞中的积累对于光动力疗法的成功是重要的，但其机制尚不清楚。我们假设一种新报道的转运蛋白，血红素载体蛋白1（HCP 1），在癌细胞中高度表达，并将卟啉转运到细胞中。我们研究了以下三个未知数：癌细胞是否通过HCP 1摄取血卟啉衍生物，HCP 1是否参与光动力疗法，以及癌细胞是否高度表达HCP 1。首先，当用血卟啉衍生物处理HCP 1过表达的细胞，然后暴露于准分子激光束时，它们发射出显著更高强度的血卟啉衍生物荧光，并且变得比对照对激光束更敏感。其次，当用血卟啉衍生物处理具有沉默的HCP 1的其他三种类型的癌细胞，然后暴露于激光束时，它们发射出明显较低强度的血卟啉衍生物荧光。第三，非癌细胞轻微表达HCP 1;另一方面，其他三种癌细胞明确表达HCP 1。这些结果表明，癌细胞通过HCP 1摄取血卟啉衍生物和HCP 1的过表达通过增加卟啉在细胞中的积累来增加光动力疗法的功效。这是关于癌细胞中卟啉转运蛋白的首次报道。
Although exogenous porphyrin accumulation in cancer cells is important for the success of photodynamic therapies, the mechanism is not clear. We hypothesized that a newly reported transporter, heme carrier protein 1 (HCP1), is highly expressed in cancer cells, and transports porphyrins into the cells. We investigated the following three unknowns: whether cancer cells take up hematoporphyrin derivative via HCP1, whether HCP1 is involved in photodynamic therapies, and whether cancer cells highly express HCP1. First, when HCP1-overexpressed cells were treated with hematoporphyrin derivative and then exposed to an eximer laser beam, they emitted a significantly higher intensity of hematoporphyrin derivative fluorescence and became more susceptible to the laser beam than control. Second, when three other types of cancer cells with silenced HCP1 were treated with hematoporphyrin derivative and then exposed to the laser beam, they emitted a significantly lower intensity of hematoporphyrin derivative fluorescence. Third, non-cancer cells slightly expressed HCP1; on the other hand, the three other types of cancer cells clearly expressed HCP1. These results indicated that cancer cells uptake hematoporphyrin derivative via HCP1 and over-expression of HCP1 increases the efficacy of photodynamic therapies by increasing porphyrin accumulation in the cells. This is the first report about a transporter of porphyrin in cancer cells.