Is There Such a Thing as a Genuine Cancer Stem Cell Marker? Perspectives from the Gut, the Brain and the Dental Pulp

SIMPLE SUMMARY: Did you ever wonder why some tissues can produce very aggressive types of cancer whereas others are apparently immune to this devastating disease? One of the most accepted theories in the scientific community states that tumors are fueled by small numbers of key master cells called cancer stem cells, which mediate tumor relapse and metastasis. Much effort has been made to identify these cells by the characterization of their defining markers, in an attempt to eliminate these cells selectively. However, many of these markers are also present in other healthy stem cells in the body, including those found in some tissues like the dental pulp, which is known to be highly resistant to carcinogenesis. This brings up the question of whether there is indeed a genuine marker that can be used to unequivocally identify cancer stem cells. We set out to address this question by a systematic comparison of healthy stem cells and cancer stem cells of different body locations, and we discuss some key factors that play a role in the resistance of certain types of stem cells to malignant transformation. ABSTRACT: The conversion of healthy stem cells into cancer stem cells (CSCs) is believed to underlie tumor relapse after surgical removal and fuel tumor growth and invasiveness. CSCs often arise from the malignant transformation of resident multipotent stem cells, which are present in most human tissues. Some organs, such as the gut and the brain, can give rise to very aggressive types of cancers, contrary to the dental pulp, which is a tissue with a very remarkable resistance to oncogenesis. In this review, we focus on the similarities and differences between gut, brain and dental pulp stem cells and their related CSCs, placing a particular emphasis on both their shared and distinctive cell markers, including the expression of pluripotency core factors. We discuss some of their similarities and differences with regard to oncogenic signaling, telomerase activity and their intrinsic propensity to degenerate to CSCs. We also explore the characteristics of the events and mutations leading to malignant transformation in each case. Importantly, healthy dental pulp stem cells (DPSCs) share a great deal of features with many of the so far reported CSC phenotypes found in malignant neoplasms. However, there exist literally no reports about the contribution of DPSCs to malignant tumors. This raises the question about the particularities of the dental pulp and what specific barriers to malignancy might be present in the case of this tissue. These notable differences warrant further research to decipher the singular properties of DPSCs that make them resistant to transformation, and to unravel new therapeutic targets to treat deadly tumors.