The cancer stem cell niche: cross talk between cancer stem cells and their microenvironment

Abstract

Despite recent progresses in tumor therapy and increased knowledge in tumor biology, tumor remains a common and lethal disease worldwide. Cancer stem cells (CSCs) are a subset of cancer cells with a stem cell-like ability, which may drive tumor growth and recurrence and are resistant to many current anticancer treatments. Solid tumors are regarded as "organs" which are comprised of cancer cells and the tumor stroma. The tumor microenvironment makes up the stroma of the tumor, which occupies the majority of the tumor mass, including the extracellular matrix (ECM), mesenchymal stem cells (MSCs), endothelial cells, immune cells, and, what is more, networks of cytokines and growth factors. The microenvironment or niche surrounding CSCs largely governs their cellular fate. Recent work has revealed that the microenvironment supports CSC self-renewal and simultaneously serves as a physical barrier to drug delivery. The tumor microenvironment plays pivotal roles in each stage of tumor development. Knowledge about the interactions of CSCs with their microenvironment would seem to be of most importance for developing new treatment strategies.

Niche interactions in epidermal stem cells

“…Cancer stem cells (CSCs) are a subset of cancer cells that demonstrate stem cell-like abilities -abilities that may induce tumor growth and tumor recurrence. CSCs also require a special "CSC niche" to regulate their stemness and proliferation, and as with endogenous stem cells, this niche prevents CSCs from being depleted [12] . Thus, the stem cell niche is a key factor in the maintenance of stem cells.…”

Progress on hypoxia-inducible factor-3: Its structure, gene regulation and biological function (Review)

“…They positively regulate the expression levels of >100 target genes, which encode protein products involved in the response to hypoxia (3)(4)(5). Tumor hypoxia was first described in the 1950s and currently there is increasing evidence to demonstrate that hypoxia is regulated by HIFs and is a common feature in several types of cancer (6)(7)(8)(9). In 1992, Semenza et al (10) identified a nuclear factor, which binds to the 3'-flanking sequence of the human erythropoietin gene (EPO) and promotes the expression of EPO under anoxic conditions.…”

Extracellular vesicles as regulators of tumor fate: crosstalk among cancer stem cells, tumor cells and mesenchymal stem cells

“…Secretion of soluble factors by tumor-surrounding cells has been described as contributing to preserving CSCs in different tumors such as glioma (53), breast cancer (54) and pancreatic cancer (55). A bidirectional exchange of genetic information between CSCs and their niche is necessary to maintain the tumor (56), and EVs together with soluble factors have recently been implicated in CSC-niche interactions ( Figure 2). …”