Proteomic profiling of cancer stem cells derived from primary tumors of HER2/Neu transgenic mice
Proteomic profiling of cancer stem cells derived from primary tumors of HER2/Neu transgenic mice
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DOI：
10.1002/pmic.201200103
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发表时间：
2012-11-01
期刊：
影响因子：
3.4
通讯作者：
Chen, Hexin
中科院分区：
文献类型：
--
作者：
Kanojia, Deepak;Zhou, Weidong;Chen, Hexin
人表皮生长因子受体 2 (HER2) 过度表达会导致乳腺肿瘤发生，其水平升高会导致癌症干细胞 (CSC) 增加、侵袭和转移。 CSC 对放射/化疗药物具有抵抗力，并且被认为是导致癌症复发的原因。 CSCs 使用基于流式细胞术的分选进行分离，虽然可靠，但该技术阻碍了 CSCs 分子靶点的方便识别。因此，为了了解 HER2 过表达导致 CSC 增加的分子因素，并为联合治疗开发有意义的靶标，我们通过方便的肿瘤球培养分离并表征了乳腺 CSC。我们使用 LC-MS/MS 鉴定了 CSC 中与非 CSC 相比蛋白质表达的改变，并使用 qRT-PCR 和蛋白质印迹证实了这些结果。铁蛋白重链1（FTH1）被确定为候选基因，其参与铁代谢，铁耗竭显着降低CSC的自我更新。我们进一步对肿瘤圈中改变的基因进行了计算机分析，并鉴定了一组代表可能的分子靶标的基因（PTMA、S100A4、S100A6、TNXRD1、COX-1、COX-2、KRT14 和 FTH1），这些基因的组合表明有望用作乳腺癌的预后标志物。
Human epidermal growth factor receptor 2 (HER2) overexpression leads to mammary tumorigenesis and its elevated levels lead to increase in cancer stem cells (CSCs), invasion, and metastasis. CSCs are resistant to radiation/chemotherapeutic drugs and are believed to be responsible for recurrence/relapse of cancer. CSCs are isolated using flow cytometry based sorting, although reliable, this technology hinders the convenient identification of molecular targets of CSCs. Therefore to understand the molecular players of increased CSC through HER2 overexpression and to develop meaningful targets for combination therapy, we isolated and characterized breast CSCs through convenient tumorsphere culture. We identified the altered protein expression in CSC as compared to non-CSC using LC-MS/MS and confirmed those results using qRT-PCR and Western blotting. Ferritin heavy chain 1 (FTH1) was identified as a candidate gene, which is involved in iron metabolism and iron depletion significantly decreased the self-renewal of CSCs. We further performed in silico analysis of altered genes in tumorsphere and identified a set of genes (PTMA, S100A4, S100A6, TNXRD1, COX-1, COX-2, KRT14, and FTH1), representing possible molecular targets, which in combination showed a promise to be used as prognostic markers for breast cancer.