Identification of a novel subpopulation of tumor-initiating cells from gemcitabine-resistant pancreatic ductal adenocarcinoma patients.
Identification of a novel subpopulation of tumor-initiating cells from gemcitabine-resistant pancreatic ductal adenocarcinoma patients.
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DOI：
10.1371/journal.pone.0081283
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hori Y
中科院分区：
文献类型：
--
作者：
Shimizu K;Chiba S;Hori Y
胰腺导管腺癌对全身化疗高度耐药。虽然有许多使用来自未接受化疗的患者的胰腺癌细胞的报道，但来自化疗耐药患者的胰腺癌细胞的特征仍不清楚。在这项研究中，我们着手在吉西他滨耐药胰腺导管腺癌患者的播散性癌细胞中建立癌细胞系。利用体外与基质细胞共培养的方法，我们建立了一种新的胰腺肿瘤起始细胞系。该细胞系需要其与基质细胞的直接相互作用，以实现其体外克隆生长和传代。它们的直接相互作用诱导基底层样细胞外基质形成，维持集落形成。该细胞系表达CD133蛋白，其表达水平自主地和通过培养条件改变。这些结果表明，存在新型胰腺肿瘤起始细胞，其需要与基质细胞直接相互作用以用于在吉西他滨耐药胰腺导管腺癌中的体外培养。这种细胞系将有助于开发新的疗法，增强吉西他滨或新的抗癌药物的效果。
Pancreatic ductal adenocarcinoma is highly resistant to systemic chemotherapy. Although there are many reports using pancreatic cancer cells derived from patients who did not receive chemotherapy, characteristics of pancreatic cancer cells from chemotherapy-resistant patients remain unclear. In this study, we set out to establish a cancer cell line in disseminated cancer cells derived from gemcitabine-resistant pancreatic ductal adenocarcinoma patients. By use of in vitro co-culture system with stromal cells, we established a novel pancreatic tumor-initiating cell line. The cell line required its direct interaction with stromal cells for its in vitro clonogenic growth and passaging. Their direct interaction induced basal lamina-like extracellular matrix formation that maintained colony formation. The cell line expressed CD133 protein, which expression level changed autonomously and by culture conditions. These results demonstrated that there were novel pancreatic tumor-initiating cells that required direct interactions with stromal cells for their in vitro cultivation in gemcitabine-resistant pancreatic ductal adenocarcinoma. This cell line would help to develop novel therapies that enhance effects of gemcitabine or novel anti-cancer drugs.
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