The cancer stem cell niche—there goes the neighborhood?

Abstract

The niche is the environment in which stem cells reside and is responsible for the maintenance of unique stem cell properties such as self-renewal and an undifferentiated state. The heterogeneous populations which constitute a niche include both stem cells and surrounding differentiated cells. This network of heterogeneity is responsible for the control of the necessary pathways that function in determining stem cell fate. The concept that cancer stem cells, a subpopulation of cells responsible for tumor initiation and formation, reside in their own unique niche is quickly evolving and it is of importance to understand and identify the processes occurring within this environment. The necessary intrinsic pathways that are utilized by this cancer stem cell population to maintain both self-renewal and the ability to differentiate are believed to be a result of the environment where cancer stem cells reside. The ability of a specific cancer stem cell niche to provide the environment in which this population can flourish is a critical aspect of cancer biology that mandates intense investigation. This review focuses on current evidence demonstrating that homeostatic processes such as inflammation, epithelial to mesenchymal transition, hypoxia and angiogenesis contribute to the maintenance and control of cancer stem cell fate by providing the appropriate signals within the microenvironment. It is necessary to understand the key processes occurring within this highly specialized cancer stem cell niche to identify potential therapeutic targets that can serve as the basis for development of more effective anticancer treatments.Stem cell populations are enriched in specific anatomical locations and require both distinctive and specific microenvironments. The niche is the microenvironment in which stem cells reside and is responsible for the maintenance of unique stem cell properties such as self-renewal and an undifferentiated state. Niches are composed of heterogeneous populations including stem cells and surrounding differentiated cells that control critical intrinsic factors necessary in determining stem cell fate. These critical factors include stromal support cells, soluble factors, extracellular matrix proteins and blood vessels. 1 The concept involving the existence and role of cancer stem cells was first described in 1994 by Lapidot et al. in a model of acute myeloid leukemia (AML). 2 To date, cancer stem cell populations have been identified in numerous solid tumors including those of the breast, 3 brain, 4 prostate, 5-7 colon, 8 pancreas 9 and liver. 10 Cancer stem cells (CSCs) are characterized by their ability to self-renew, differentiate and initiate tumors. [10][11][12] The concept of a CSC niche is derived from the similarities that exist between normal stem cells and CSCs. The signaling pathways utilized by both normal stem cells and CSCs overlap and are based on embryonic signaling pathways which allow self-renewal. To date, our understanding regarding stem cell regulation has expanded due to intense inves...

Emerging Roles of Krüppel-Like Factor 4 in Cancer and Cancer Stem Cells

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Darwinian Principles in Cancer Therapy

“…It seems generally agreed upon that somatic mutations and other forms of evolutionary pressure, such as the niche effect, 20 can lead to tumour heterogeneity that even extends to the highest hierarchical order, that of tumour stem cell. 21 Our therapeutic decisions are invariably based on the (molecular) histological features of the dominant, i.e.…”

Deciphering the Key Features of Malignant Tumor Microenvironment for Anti-cancer Therapy

“…There are 2 types of CSC niches, osteoblast CSC niche and vascular CSC niche, that regulate CSC self-renewal and differentiation [3,10]. The niches consist of CSCs, stromal cells, and blood vessels.…”

“…In addition, aggressive tumor cells (such as cancer stem cells) are important in the initiation and development of a malignant TME by active participation in tumor neovascularization and generation of a cancer stem cell niche [9][10][11]. Although stromal cells are considered a promoter during the genesis of the TME [12], dysfunction of stromal cells may induce generation of cancer stem cells and malignant tumors [13].…”