The Cancer Stem Cell Hypothesis: A Guide to Potential Molecular Targets

Abstract

Common cancer theories hold that tumor is an uncontrolled somatic cell proliferation caused by the progressive addition of random mutations in critical genes that control cell growth. Nevertheless, various contradictions related to the mutation theory have been reported previously. These events may be elucidated by the persistence of residual tumor cells, called Cancer Stem Cells (CSCs) responsible for tumorigenesis, tumor maintenance, tumor spread, and tumor relapse. Herein, we summarize the current understanding of CSCs, with a focus on the possibility to identify specific markers of CSCs, and discuss the clinical application of targeting CSCs for cancer treatment.

Clinical translation for endometrial cancer stem cells hypothesis

“…Another hypothesis is that normal stem cells have similar location as CSC and a niche signal from normal stem cells induces CSC [37]. Some authors have shown that CSC phenotype can be acquired by tumor cells that have previously negative stem cell markers [35]. More recently, it has been defended a dedifferentiation of non-CSC into CSC, a similar phenomenon described in somatic cells that can be dedifferentiated to the pluripotent cells [38].…”

“…This theory points the presence of a subpopulation that initiates and develops the tumor [34]. CSC are recognized as responsible for tumorigenesis, tumor differentiation, tumor maintenance, tumor spread, and tumor relapse [35]. Self-renewal capacity is regulated by several pathways, namely Wnt, Notch, and Hedgehog.…”

“…CSC can be isolated by surface markers, can form spheres in vitro, and are tumorigenic in vivo even at a low proportion of cells [34,35,39]. In the last decade, studies have emerged in the demand of a surface marker that could identify these cells.…”

“…Several proteins have been pointed as potential markers in different types of tumors. One of the surface antigens studied was CD133, also described as PROML1 or prominin, which has been used in different types of solid cancers like lung, brain, liver, colon, and prostate cancer [35].…”

Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging

“…13,14 The selection of mAb directed at surface antigens expressed by tumor cells has enabled the development of new reagents for diagnostic purposes or for targeted therapies. 15,16 Magnetic resonance imaging (MRI) is a well-recognized tool for in vivo cell tracking because of its high spatial and contrast resolution, as well as its reproducibility. Combined with an advanced contrast agent, MRI allows for molecular profiling of target tissues/cells and can enable the early detection of malignancies, making more accurate staging and treatment monitoring possible.…”