Stem cells are undifferentiated cells that renew themselves while simultaneously producing differentiated tissue- or organspecific cells through asymmetric cell division. The appreciation of the importance of stem cells in normal tissue biology has prompted the idea that cancers may also develop from a progenitor pool (the “cancer stem cell (CSC) hypothesis”), and this idea is gaining increasing acceptance among scientists. CSCs are sub-populations of cancer cells responsible for tumor initiation, differentiation, recurrence, metastasis, and drug resistance. First identified in the hematopoietic system, CSCs have also been discovered in solid tumors of the breast, colon, pancreas, and brain. Recently, the tissue-specific stem cells of the normal urothelium have been proposed to reside in the basal layer, and investigators have isolated phenotypically similar populations of cells from urothelial cancer cell lines and primary tumors. Herein, we review the CSC hypothesis and apply it to explain the development of the two different types of bladder cancer: noninvasive (“superficial”) carcinoma and invasive carcinoma. We also examine potential approaches to identify CSCs in bladder cancer as well as therapeutic applications of these findings. While exciting, the verification of the existence of CSCs in bladder cancer raises several new questions. Herein, we identify and answer some of these questions to help readers better understand bladder cancer development and identify reasonable therapeutic strategy for targeting stem cells.
Keywords: Bladder cancer, cancer stem cell, miRNA, EMT, superficial, muscle invasive, noninvasive tumors, superficial tumors, muscle, heterogeneity, drug resistance, tumor-initiating cell, melanomas, prostate cancer, colon cancer, chronic myeloid leukemias, head and neck squamous cell carcinoma, pancreatic cancer, spleen, colony-forming cells, nonpolarity, potency, embryonic stem cells, nonembryonic stem cells, stem cells, multipotent, cell death, blastocyst, protein-encoding, core circuitry, genes, apoptosis, plasticity, signaling pathways, epidermal precursors, organic molecules, ATP-binding cassette, flow cytometry, side population assay, isolate stem cells, renal pelvis, urothelium, transitional epithelium, binucleate, polipoid nature, umbrella cells, toxic materials, isolation of human bladder, tissues, distinct cell types, tumorigenesis, chromosomal disorders, egg fuse, zygote, mononucleated myoblasts, chromosomal aberrations, aneuploidy, dehydrogenase isoform, stemness, cellular detoxification, oxidation of aldehydes, squamous cancer, self-renewal transcription factors, Transition Between Epithelial and Mesenchymal Phenotype, multistep process, apical-basal polarity, lymphatic vessels, blood circulation, migration of cells, tumor-stroma interface, transcription factors, ovarian cancer, posttranscriptional stage, dicer-null, target binding sites, basal lamina, immunohistochemistry, mesoderm lineages, oncogenic/stem cell transcription, genomic sequence, radiotherapeutic measures, cell-context-dependent manner, clinical realm