Pluripotent human stem cell lines: what we can learn about cancer initiation.
Although the cancer stem cell (CSC) hypothesis has become an attractive model to account for tumor recurrence, failure to define a cell of origin has created the need to explore alternative models for cancer initiation and maintenance. Recent studies have linked an embryonic stem cell (ESC)-like gene signature with poorly defined high-grade tumors. Here, we review advances in the ESC field with an emphasis on how human pluripotent stem cells (hPSCs) can be used to define early tumorigenic events, including potential miRNA and epigenetic targets, as well as proto-oncogene and tumor suppressor networks that might facilitate hierarchal transformation. These studies allow for investigation of cancer initiation in a manner that cannot be achieved using primary tumors, where only retrospective evaluation of CSC development is possible. By comparing transformed hPSCs with their normal counterparts, we hope to develop novel cell-specific therapies that selectively target CSCs.
Werbowetski-Ogilvie
Tamra E
TE
McMaster Stem Cell and Cancer Research Institute, 1200 Main St. West, Hamilton, Ontario L8N 3Z5, Canada.
Bhatia
Mickie
M
D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D054278:Embryonal Carcinoma Stem Cells; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D009373:Neoplasms, Germ Cell and Embryonal / Q000473:pathology / Q000503:physiopathology; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology; D009857:Oncogenes; D039904:Pluripotent Stem Cells / Q000502:physiology*; D000090063:Proto-Oncogene Mas
C000715470:MAS1 protein, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas