Abstract

Cancer stem cells (CSCs) are a small subset of cancer cells responsible for maintenance and progression of several types of cancer. Isolation, propagation, and the differentiation of CSCs in the proper stem niches expose the intrinsic difficulties for further studies. Here we show that induced cancer like stem cells (iCLSCs) can be generated by in vitro oncogenic manipulation of mouse embryonic stem cells (mESCs) with well-defined oncogenic elements; SV40 LTg and HrasV12 by using a mouse stem virus long terminal repeat (MSCV-LTR)-based retroviral system. The reprogrammed mESCs using both oncogenes were characterized through their oncogenic gene expression, the enhancement of proliferation, and unhampered maintenance of stem properties in vitro and in vivo. In addition, these transformed cells resulted in the formation of malignant, immature ovarian teratomas in vivo. To successfully further expand these properties to other organs and species, more research needs to be done to fully understand the role of a tumor- favorable microenvironment. Our current study has provided a novel approach to generate induced cancer like stem cells through in vitro oncogenic reprogramming and successfully initiated organ-specific malignant tumor formation in an orthotopic small animal cancer model.

Highlights

  • The hierarchical theory of the organization of cancer suggests that only a small subset of cells is responsible for the initiation and further growth of cancer [1,2,3]

  • The present study demonstrates that mouse embryonic stem cells can be reprogramed into induced cancer like stem cells by introduction of well defined oncogenic elements, (the simian virus 40 large T oncogene (SV40 large T antigene (LTg)) and an oncogenic ras (HrasV12)) by using a mouse stem virus long terminal repeat (MSCV-LTR)-based retroviral plasmid

  • Retroviral infection of mouse embryonic stem cells (mESCs) seems highly dependent on viruses generated from different types of retroviral plasmids

Read more

Summary

Introduction

The hierarchical theory of the organization of cancer suggests that only a small subset of cells is responsible for the initiation and further growth of cancer [1,2,3]. Those small populations of cells have been defined as cancer stem cells (CSCs). CSCs exhibit features such as self-renewal and the ability of differentiation into heterogeneous and tumorigenic cancer cells [1, 4]. The tumorigenic potential of these cells has been demonstrated in various xenograft studies using immune compromised mice [5, 6, 10]. Further characterization of CSCs’ properties and capabilities have been hampered by PLOS ONE | DOI:10.1371/journal.pone.0141172 October 21, 2015

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call