Overview of Cancer Stem Cells (CSCs) and Mechanisms of Their Regulation: Implications for Cancer Therapy

Abstract

The identification of small subpopulations of cancer stem cells (CSCs) from blood mononuclear cells in human acute myeloid leukemia (AML) in 1997 was the landmark observation for recognizing the potential role of CSCs in tumor aggressiveness. Two critical properties contribute to the functional role of CSCs in the establishment and recurrence of cancerous tumors: their self-renewal capacity and their potential to differentiate into unlimited heterogeneous populations of cancer cells. These findings suggest that CSCs may represent novel therapeutic targets for the treatment and/or prevention of tumor progression as they appear to be involved in cell migration, invasion, metastasis, and treatment resistance, all of which lead to poor clinical outcomes. The identification of CSC-specific markers, the isolation and characterization of CSCs from malignant tissues, and targeting strategies for the destruction of CSCs provides a novel opportunity for cancer research. Described in this overview is the potential implication of several common CSC markers in the identification of CSC subpopulation restricted to common malignant diseases e.g., leukemia, breast, prostate, pancreatic and lung cancers. The role of microRNAs (miRNAs) in the regulation of CSC function is also discussed, as are several methods commonly used in CSC research. The potential role of the anti-diabetic drug metformin that has been shown to have effects on CSCs, and known function as an anti-tumor agent, provides an example of this new class of chemotherapeutics.

New insights into pancreatic cancer stem cells

“…Pancreatic CSC populations account for less than 1% of all pancreatic cancer cells [14] . The pancreatic CSCs identified so far are CD133, CD24, CD44, EPCAM, ESA, c-Met, Aldh1, and more recently DclK1 and Lgr5 [9][10][11][12][13][14][15][16][17][18] . These pancreatic CSC markers are well known based on several xenograft studies.…”

“…All these markers may mark themselves or co-express to show the CSC properties [19][20][21] . CD133 pancreatic CSC cells co-express the CXCR4 receptor at the invading margins of human pancreatic ductal tumors [14,19] . Other CSC markers that co-express (CD24 + /CD44 + /EPCAM and CD133 + ) show CSC properties making them often resistant to chemo and radiotherapy.…”

“…Cancer stem cell (CSC) research has achieved much progress in a variety of solid tumors, including pancreatic cancer to some extent [11] . The identification of specific cell surface markers enabled purification of CSCs from different cell lines or clinical tissues/samples, leading to evaluate the nature of CSCs [12][13][14] . Understanding of pancreatic CSCs may improve existing therapies and deepen insight into the role of CSCs in pancreatic cancer progression [11] .…”

Heterogeneity of tumor chemosensitivity in ovarian epithelial cancer revealed using the adenosine triphosphate-tumor chemosensitivity assay

“…Previous studies have demonstrated that tumors originate from cancer stem cells (4). However, the continuous differentiation of stem cells during the process of tumor growth results in daughter cells with variations in their genetic and molecular characteristics following several rounds of proliferation, leading to differences in tumor growth, invasiveness, drug susceptibility and prognosis (5).…”

Double-Staining Immunohistochemistry of Stem Cell Markers in Human Liver Cancer Tissues

“…Typically, there is a very small population of stem cells and cancer stem cells (CSCs) in normal and cancerous tissues, respectively [2]. Hence, IHC has several advantages over IF technique including: 1) capability of being repeatedly used in order to search for few positive cells, 2) no reduction in signal intensity, 3) provides superior morphological information, and 4) could be utilized to distinguish between normal and cancerous tissue.…”