Reprogramming of prostate cancer-associated stromal cells to embryonic stem-like

Abstract

Background: CD90(+) prostate cancer-associated (CP) stromal cells represent a diseased cell type found only in tumor tissue. They differ from their normal counterpart in gene expression and inductive signaling. Genetic reprogramming by induced pluripotent stem (iPS) cell technology can effectively change adult cells into stem-like cells through wholesale alteration of the gene expression program. This technology might be used to 'erase' the abnormal gene expression of diseased cells. The resultant iPS cells would no longer express the disease phenotype, and behave like stem cells.

Methods: CP stromal cells, isolated from tumor tissue of a surgically resected prostate by anti-CD90-mediated sorting and cultured in vitro, were transfected with in vitro packaged lentiviral expression vectors containing stem cell transcription factor genes POU5F1, LIN28, NANOG, and SOX2.

Results: Alkaline phosphatase-positive iPS cells were obtained in about 3 weeks post-transfection at a frequency of 10(-4) . Their colony morphology was indistinguishable from that of human embryonic stem (ES) cells. Transcriptome analysis showed a virtually complete match in gene expression between the iPS and ES cells.

Conclusions: Genes of CP stromal cells could be fully inactivated by genetic reprogramming. As a consequence, the disease phenotype was 'cured'.