Cancer stem cells are thought to be the source of some types of primary and recurrent cancers and are characterized by their high degree of potency and self-renewing capacity. In embryonic stem cells and germ cells, properties of self-renewal and pluripotency are regulated by the Oct4A gene, a marker which has been suspected of playing a role in the origin of some cancers. Although a number of key questions still remain unanswered, scientists have now made important progress in understanding how the Oct4A gene might be involved in the development of prostate cancer.
Led by Dr. Paula Sotomayor, researchers in the Department of Urologic Oncology at the Roswell Park Cancer Institute in Buffalo, New York have identified Oct4A in a small subset of prostate cells which were negative for many other types of more conventional cancer stem cells markers, such as markers of luminal epithelial and basal epithelial cell differentiation, including the markers ABCG2, NANOG, CD133 and AMACR. A further subpopulation of the cells expressing Oct4A were also found to co-express the embryonic stem cell marker Sox2, which is a transcription factor necessary for the self-renewal of undifferentiated cells. Yet another subpopulation was found to co-express synaptophysin, while the majority of the Oct4A-expressing cells were found to co-express chromagranin A, both of which are neuroendocrine differentiation markers.
Cells expressing Oct4A have been found in both benign and malignant prostate glands. As one would expect, the amount of Oct4A-expressing cells that are present in the gland is directly correlated with the Gleason score, which is a measure of glandular size and microscopic appearance of the prostate, with lower scores being associated with smaller, more tightly packed glands, whereas higher scores indicate a more loosely dispersed glandular structure.
Oct4A is one variant, along with Oct4B, of the Oct4 marker, and the precise molecular mechanisms governing these variants are yet to be determined. As the authors describe in their publication, “rare cells that express Oct4 were identified in several somatic cancers, however, the differential contributions of the Oct4A and Oct4B variants were not determined.”
Nevertheless, with the discovery that cells expressing Oct4A are present in cancerous prostates in numbers that correlate with the severity of the malignancy, scientists are one step closer to understanding this particular form of cancer. Further investigations will be focused especially on those various subpopulations of the cells that co-express the neuroendocrine differentiation markers chromagranin A and synaptophysin, both of which offer new and important pieces in the puzzle.