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.
Highlights
Despite the significant progress in our understanding of cancer proliferation and genomics, there has been little progress in understanding cancer origins and early development
The morphology of the P-element induced wimpy testis like 2 (PIWIL2)-GFP transfected fibroblasts expressing GFP gradually changed from a typical long spindle shape to a small spherical shape (Figure 3a, 3b)
By 3 weeks posttransfection all the PIWIL2-GFP transfected fibroblasts assumed the spherical morphology (Figure 3c, 3d), and among these cells spheroid like colonies appeared (Figure 3e-3h)
Summary
Despite the significant progress in our understanding of cancer proliferation and genomics, there has been little progress in understanding cancer origins and early development. No matter what mechanism is involved, carcinogenesis results in the formation of a pool of tumorigenic cells capable of self-renewal, rapid proliferation, differentiation and ability to metastasize from the point of origin. A pivotal role for the involvement of tumorigenic cancer stem cells (CSCs) [2, 3] in recurrence and metastasis has been proposed. The CSCs are subpopulations of cells within a tumor that are involved in cancer initiation, maintenance, and propagation [4, 5]. It is highly desirable to be able to generate cell lines in vitro that can be used to clarify genetic mechanisms and malignant transformation pathways that lead to tumor development. In turn studying in vitro induced tumorigenic cell (ITGC) lines may promote the development of new clinically relevant cancer therapies
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