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转染Piwil2的人成纤维细胞具有癌症干细胞样特性且基因不稳定。

Piwil2-transfected human fibroblasts are cancer stem cell-like and genetically unstable.

作者信息

Zhang Deying, Wu Xin, Liu Xing, Cai Chunhong, Zeng Guangping, Rohozinski Jan, Zhang Yuanyuan, Wei Guanghui, He Dawei

机构信息

Department of Urology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China.

Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, North Carolina 27103, USA.

出版信息

Oncotarget. 2017 Feb 14;8(7):12259-12271. doi: 10.18632/oncotarget.14696.

DOI:10.18632/oncotarget.14696
PMID:28103575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5355342/
Abstract

Uncontrolled cell proliferation and inhibition of apoptosis are considered to be vital for cancer initiation, maintenance, infiltration, metastasis and recurrence after anti-cancer therapy. Here we report the generation of a novel cell line by reprogramming child foreskin fibroblast with the full length apoptosis inhibitor gene PIWIL2. The fibroblasts transfected with PIWIL2 expressed the stem cell markers OCT-4, NANOG, SOX-2, KLF-4 and C-MYC; endoderm marker AFP and GATA6; mesoderm markers ACTA2 and BRACHYURY; and ectoderm markers NESTIN and TUBB3. The karyotype was found to be hyperdiploid. The PIWIL2 transfected fibroblast cells grew into tumorous masses within 5 weeks of subcutaneous injection into adult nude mice. Although the injected cell expressed markers for all three germlines, ectoderm, mesoderm, and endoderm, they did not form teratomas in vivo. This study indicates that the PIWIL2 gene could play a key role in cancer induction and maintenance. This method for generating induced tumorigenic cells (ITGC) provides a new research tool to study oncogenesis that in turn may lead to a better understanding of cancer etiology and the development of novel anti-cancer therapies.

摘要

不受控制的细胞增殖和细胞凋亡抑制被认为对癌症的起始、维持、浸润、转移以及抗癌治疗后的复发至关重要。在此，我们报告通过用全长凋亡抑制基因PIWIL2对儿童包皮成纤维细胞进行重编程而产生一种新型细胞系。用PIWIL2转染的成纤维细胞表达干细胞标志物OCT-4、NANOG、SOX-2、KLF-4和C-MYC；内胚层标志物AFP和GATA6；中胚层标志物ACTA2和BRACHYURY；以及外胚层标志物NESTIN和TUBB3。发现其核型为超二倍体。将PIWIL2转染的成纤维细胞皮下注射到成年裸鼠体内后，在5周内长成肿瘤块。尽管注射的细胞表达了外胚层、中胚层和内胚层这三个胚层的标志物，但它们在体内并未形成畸胎瘤。本研究表明PIWIL2基因可能在癌症诱导和维持中起关键作用。这种产生诱导致瘤细胞（ITGC）的方法为研究肿瘤发生提供了一种新的研究工具，进而可能有助于更好地理解癌症病因并开发新型抗癌疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/7d8c5ac2a1ba/oncotarget-08-12259-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/7f7a24d71a49/oncotarget-08-12259-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/38eea4209a5f/oncotarget-08-12259-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/af9c3d6a1d9c/oncotarget-08-12259-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/ba5729f59bad/oncotarget-08-12259-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/0b5943288792/oncotarget-08-12259-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/6aa460a25c73/oncotarget-08-12259-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/c0613ae51755/oncotarget-08-12259-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/2cd1e2c6f515/oncotarget-08-12259-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/7d8c5ac2a1ba/oncotarget-08-12259-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/7f7a24d71a49/oncotarget-08-12259-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/38eea4209a5f/oncotarget-08-12259-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/af9c3d6a1d9c/oncotarget-08-12259-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/ba5729f59bad/oncotarget-08-12259-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/0b5943288792/oncotarget-08-12259-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/6aa460a25c73/oncotarget-08-12259-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/c0613ae51755/oncotarget-08-12259-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/2cd1e2c6f515/oncotarget-08-12259-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/943a/5355342/7d8c5ac2a1ba/oncotarget-08-12259-g009.jpg

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