Cancer Stem Cell Hierarchy Defines Bladder Cancer Subtypes That Predict Survival

摘要

It is well established that most, if not all, human adult organs consist of tissue-specific stem cells that can self-renew and give rise to progenitors with increasingly limited developmental potential, ultimately, terminally differentiated cells. All malignancies develop from cells within such an adult tissue developmental hierarchy, and require multiple epige-netic and genetic alterations resulting in malignant cells capable of proliferating uncontrollably, surviving under constant immunosurveillance, and eventually metastasizing to distal organs. It is within this context that the cancer stem cell (CSC) hypothesis has emerged, proposing the existence of a pure CSC located at the apex of a hierarchical tumor organization, which can self-renew and differentiate stepwise into developmentally related tumor populations. It should be noted that the CSC hypothesis does not rule out the co-existence of clonal evolution that tumor cells are constantly under selective pressure. It is possible that more than one clone of CSC may coexist within a tumor specimen.