Microarray Analysis Identifies a Unique Molecular Signature of Human Thyroid Cancer Stem Cells

Abstract

Anaplastic thyroid cancer (ATC) is the most lethal type of thyroid cancer, with a mean survival of six months from the time of diagnosis. Using patient-derived ATC cell lines, we have recently shown that ATC contains a minority population of cancer stem cells that can grow as self-renewing, non-adherent thyrospheres. Compared to bulk tumor cells raised in monolayers, these thyrospheres have increased clonogenic and tumor-initiating potential, and they robustly initiate tumors that closely resemble human ATC when orthotopically implanted into the thyroids of immunodeficient mice. Here we use the Affymetrix GeneChip analysis to identify gene expression differences between thyrospheres and monolayer cells from the human ATC cell line THJ-11T. Our microarray analysis identified a total of 1,659 differentially expressed gene transcripts, many of which have been implicated in key pathways such as those governing cell proliferation, migration, invasion, vasculogenesis, and chemoresistance. These results indicate that thyroid cancer stem cells have a distinct molecular signature. These data will be helpful for the design of future therapeutic strategies that directly target thyroid cancer stem cells.