Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): A new approach to finding targets for cervical cancer stem cell treatment.
Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): A new approach to finding targets for cervical cancer stem cell treatment.
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DOI：
10.18632/oncotarget.16783
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发表时间：
2017-06-20
期刊：
影响因子：
--
通讯作者：
Fujii T
中科院分区：
文献类型：
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作者：
Sato M;Kawana K;Adachi K;Fujimoto A;Yoshida M;Nakamura H;Nishida H;Inoue T;Taguchi A;Ogishima J;Eguchi S;Yamashita A;Tomio K;Wada-Hiraike O;Oda K;Nagamatsu T;Osuga Y;Fujii T
宫颈储备细胞是上皮祖细胞，在病理学上明显是宫颈癌的起源。因此，研究宫颈储备细胞的特征可以深入了解宫颈癌干细胞（CSC）的特征。在这项研究中，我们建立了一种从人类诱导多能干细胞（iPSC）中再生宫颈储备细胞样特性的方法，并将这些细胞命名为诱导储备细胞样细胞（iRCs）。大约 70% 的 iRC 储备细胞标记物 p63、CK5 和 CK8 呈阳性。 iRC 还表达 SC 连接标记 CK7、AGR2、CD63、MMP7 和 GDA。虽然 iRC 既不表达 ERα 也不表达 ERβ，但它们表达 CA125。这些数据表明iRCs具有宫颈上皮祖细胞的特征。与正常宫颈上皮细胞相比，iRCs 分泌更高水平的多种炎症细胞因子，如巨噬细胞迁移抑制因子 (MIF)、可溶性细胞间粘附分子 1 (sICAM-1) 和 C-X-C 基序配体 10 (CXCL-10)。 iRC 还表达人类白细胞抗原-G (HLA-G)，它是免疫耐受和癌发生的重要细胞表面抗原。加上宫颈 CSC 可以起源于储备细胞这一事实，我们的数据表明 iRC 是有效的免疫调节剂，可能有利于宫颈癌细胞的存活。总之，通过从 iPSC 中产生储备细胞样特性，我们提供了一种新方法，可以对宫颈癌干细胞产生新的见解，并帮助找到新的致癌靶点。
Cervical reserve cells are epithelial progenitor cells that are pathologically evident as the origin of cervical cancer. Thus, investigating the characteristics of cervical reserve cells could yield insight into the features of cervical cancer stem cells (CSCs). In this study, we established a method for the regeneration of cervical reserve cell-like properties from human induced pluripotent stem cells (iPSCs) and named these cells induced reserve cell-like cells (iRCs). Approximately 70% of iRCs were positive for the reserve cell markers p63, CK5 and CK8. iRCs also expressed the SC junction markers CK7, AGR2, CD63, MMP7 and GDA. While iRCs expressed neither ERα nor ERβ, they expressed CA125. These data indicated that iRCs possessed characteristics of cervical epithelial progenitor cells. iRCs secreted higher levels of several inflammatory cytokines such as macrophage migration inhibitory factor (MIF), soluble intercellular adhesion molecule 1 (sICAM-1) and C-X-C motif ligand 10 (CXCL-10) compared with normal cervical epithelial cells. iRCs also expressed human leukocyte antigen-G (HLA-G), which is an important cell-surface antigen for immune tolerance and carcinogenesis. Together with the fact that cervical CSCs can originate from reserve cells, our data suggested that iRCs were potent immune modulators that might favor cervical cancer cell survival. In conclusion, by generating reserve cell-like properties from iPSCs, we provide a new approach that may yield new insight into cervical cancer stem cells and help find new oncogenic targets.