探討鐵代謝在人類攝護腺癌細胞轉移中所扮演的角色

Abstract

血清中鐵離子濃度的代謝異常是臨床上癌症病人常見的併發症，並且亦有文獻指出鐵離子的代謝和人類癌症的進程有很大的關係，然而迄今鐵離子的代謝對人類前列腺癌在進程與侵襲能力上的影響仍不清楚。因此在本篇研究當中，我們嘗試探尋鐵離子對於攝護腺癌細胞在細胞存活與侵襲能力上的影響。從生物資料庫的分析顯示預後較差的攝護腺癌病人擁有較低的運鐵素表現量。此外，在我們的研究結果中也發現能過量表達鐵調素的攝護腺癌細胞的細胞培養液亦能促進其他攝護腺癌細胞的侵襲能力，顯示鐵條素確實會促進人類癌細胞的移動能力。此外，從外加三價鐵離子的實驗中我們出乎意料地發現鐵離子會抑制攝護腺癌細胞的侵襲能力並降低細胞內活性含氧物的量，並且不論是鐵調素或三價鐵離子都不會對基質金屬蛋白酵素9有顯著的影響。經由這些實驗結果顯示調控鐵的賀爾蒙鐵調素可以促進攝護腺癌細胞的侵襲能力，而三價的鐵離子則是會降低細胞的移動與活性含氧物的量，這些結果都指出鐵調素所誘導引發的攝護腺癌細胞侵襲能力增加的現象可能是經由一個和鐵離子不相關的路徑所導致的。

Dysregulation of iron levels in sera has been often observed in various cancer patients and has been proposed that alteration of iron metabolism may play an important role in human cancer progression. However, the involvement of iron metabolism in prostate cancer cell invasion and progression is still unclear. In this study, I addressed whether iron metabolism played a role in prostate cancer cell viability and invasion. The results from the bioinformatics analysis from a public database showed that the low expression level of ferroportin was associated with poor prognosis of human prostate cancer patients. Moreover, our results showed that the conditioned media of the hepcidin-overexpressing cells could increase prostate cancer cell invasion, suggesting that hepcidin can induce human cancer cell motility. On the other hand, the results unexpectedly showed that the treatment of ferric iron reduced prostate cancer cell invasion and the cellular level of ROS. Both hepcidin and ferric ion treatments had no significant effects on metalloproteinase 9. The results together indicate that iron-hormone hepcidin exhibits an induction effect on prostate cancer cell invasion, and ferric ion treatment reduces prostate cancer cell motility and ROS. The data suggest that hepcidin-induced prostate cancer cell invasion may be through an iron-independent pathway.