Design and Characterization of Bioengineered Cancer-Like Stem Cells.
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.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Salt Lake City, Utah, United States of America.
Sungpil
S
Cho
Department of Bioengineering, Salt Lake City, Utah, United States of America.
Hongsuk
H
Park
Department of Pathology, Salt Lake City, Utah, United States of America.
Elke A
EA
Jarboe
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Salt Lake City, Utah, United States of America.
C Matthew
CM
Peterson
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, United States of America.
You Han
YH
Bae
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Salt Lake City, Utah, United States of America.
Margit M
MM
Janát-Amsbury
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D014411:Neoplastic Stem Cells / Q000502:physiology*; D009857:Oncogenes / Q000502:physiology; D012190:Retroviridae / Q000378:metabolism; D020079:Terminal Repeat Sequences / Q000235:genetics; D059016:Tumor Microenvironment / Q000502:physiology