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

// Deying Zhang 1, * , Xin Wu 1, * , Xing Liu 1 , Chunhong Cai 1 , Guangping Zeng 1 , Jan Rohozinski 2, 3 , Yuanyuan Zhang 2 , Guanghui Wei 1 Dawei He 1 1 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 2 Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, North Carolina 27103, USA 3 Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA * These authors have contributed equally to this work Correspondence to: Dawei He, email: dw.he@163.com Keywords: piwil2, fibroblast, gene transfection, cancer stem cell, oncogenesis Received: July 25, 2016      Accepted: December 27, 2016      Published: January 17, 2017 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.