However, it is possible that accumulation of genetic mutations within a differentiated or progenitor cell can allow expression of stem cell behavior, and that this may provide an alternative source of CSCs

However, it is possible that accumulation of genetic mutations within a differentiated or progenitor cell can allow expression of stem cell behavior, and that this may provide an alternative source of CSCs. cancer-related mortality, with an estimated 500 000 new cases diagnosed yearly [1]. For the past several decades the mainstay of treatment for HNSCC has been surgery and external beam radiation. More recent clinical trials have demonstrated the benefit of combining chemotherapy and radiation for Mouse monoclonal to CD34.D34 reacts with CD34 molecule, a 105-120 kDa heavily O-glycosylated transmembrane glycoprotein expressed on hematopoietic progenitor cells, vascular endothelium and some tissue fibroblasts. The intracellular chain of the CD34 antigen is a target for phosphorylation by activated protein kinase C suggesting that CD34 may play a role in signal transduction. CD34 may play a role in adhesion of specific antigens to endothelium. Clone 43A1 belongs to the class II epitope. * CD34 mAb is useful for detection and saparation of hematopoietic stem cells advanced stage disease, leading to modest improvements in treatment outcomes [15]. Despite this recent improvement, the increase in overall survival has been nominal and cancer recurrence and treatment failures continue to occur in a significant percentage of patients. The biology underpinning why some tumors respond favorably to treatment and others do not is largely unknown. Over the last 15 years, advances in tumor biology have led to the discovery that many cancers, including HNSCC, appear to be supported by cells with stem-like properties. Studies in a wide variety of malignancies have demonstrated that only a distinct subpopulation of tumor cells, termed cancer stem cells (CSCs), contain the ability to undergo AS 602801 (Bentamapimod) self-renewal and differentiation (properties of normal stem cells) and hence have the ability to initiate tumorigenesis and support ongoing tumor growth. Furthermore, it appears that, like their normal stem cell counterparts, CSCs have increased resistance to standard cytotoxic therapies. These findings have coalesced into the cancer stem cell theory of tumorigenesis, which has remarkable implications on our understanding of tumor initiation, disease progression, and treatment response. Here we review the basics of the cancer stem cell theory as it applies to HNSCC. == 2. Emergence of the Cancer Stem Cell Theory == The cellular and molecular requirements for initiation of tumorigenesis are a series of mutations resulting in the acquisition of replication and growth-factor independence, resistance to growth-inhibitory signals, tissue invasion, and metastasis [6]. The mechanisms underlying these mutations have been extensively interrogated; however a unifying model of tumorigenesis remains to be completely elucidated. Tumors have long been recognized to consist of a heterogeneous population of cells differing in proliferative capacity, histologic and immunophenotypic appearance, and tumorigenic potential. Traditionally, this heterogeneity has been hypothesized to be the result of the stochastic accumulation of numerous and varied individual mutations and microenvironmental signals that provide a selective advantage to certain tumor cells. Over the last several years however, a new hypothesis has emerged suggesting that tumor heterogeneity is supported by a stem cell hierarchy. The cancer stem cell hypothesis postulates that tumor heterogeneity with regards to initiation, progression, response to therapy, and metastasis is the result of mutations which either render a normal somatic tissue stem cell cancerous, or AS 602801 (Bentamapimod) cause a cancer cell to become stem cell-like [7]. This AS 602801 (Bentamapimod) mutated CSC is then capable of giving rise both to additional CSCs and to a variety of more differentiated and functionally divergent cancer cells, much like a normal somatic tissue stem cell. Unlike in the traditional stochastic tumorigenesis model, the CSC model proposes that tumorigenicity resides in only a small subpopulation of cancer cells and that these cells, rather than the bulk of the tumor, are responsible for tumor initiation and growth (Figure 1). == Figure 1. == CSC Theory. (a) Origin of CSC. CSC may originate from endogenous stem cells (SC) or reprogramming of the transit amplifying (TA) or differentiated (Diff) cell population. (b) The CSC theory proposes a tumor cell hierarchy with the CSC at the apex. Only CSCs are able to give rise to new tumors and provide support for ongoing tumor growth (Green: CSC, AS 602801 (Bentamapimod) Red: Transit amplifying population, Pink: differentiated cell population). As with normal somatic stem cells, CSCs are defined by their ability to self-renew and to give rise to a heterogeneous population of tumor cells. This population of tumor cells consists of rapidly dividing cells (similar to the transient amplifying (TA) cell population in normal tissue) as well as additional CSCs and more.