Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

Abstract

Stemness combines the ability of a cell to perpetuate its lineage, to give rise to differentiated cells, and to interact with its environment to maintain a balance between quiescence, proliferation, and regeneration. While adult Stem Cells display these properties when participating in tissue homeostasis, Cancer Stem Cells (CSCs) behave as their malignant equivalents. CSCs display stemness in various circumstances, including the sustaining of cancer progression, and the interaction with their environment in search for key survival factors. As a result, CSCs can recurrently persist after therapy. In order to understand how the concept of stemness applies to cancer, this review will explore properties shared between normal and malignant Stem Cells. First, we provide an overview of properties of normal adult Stem Cells. We thereafter elaborate on how these features operate in CSCs. We then review the organization of microenvironment components, which enables CSCs hosting. We subsequently discuss Mesenchymal Stem/Stromal Cells (MSCs), which, although their stemness properties are limited, represent essential components of the Stem Cell niche and tumor microenvironment. We next provide insights of the therapeutic strategies targeting Stem Cell properties in tumors and the use of state-of-the-art techniques in future research. Increasing our knowledge of the CSCs microenvironment is key to identifying new therapeutic solutions.

TGF-β1 secreted by pancreatic stellate cells promotes stemness and tumourigenicity in pancreatic cancer cells through L1CAM downregulation

“…Here, we show that L1CAM low PDAC cells (either L1 sorted or shL1) are less differentiated and have an enhanced CSC phenotypes, including self-renewal, tumour initiation, migration, invasion and chemoresistance. Selfrenewal capacity, undifferentiated state and capability to differentiate into heterogeneous population of differentiated cancer cells represent hallmarks of CSCs [40].…”

Isolation and Identification of Cancer Stem-Like Cells in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Pilot Study

“…An enrichment of CSCs in the ALDH high population was also described in NSCLC patients and cell lines (52). In addition, several key regulators have been described as essential for the maintenance of a progenitor cell state under both normal and cancerous conditions (e.g., SOX2 and the homeobox protein NANOG) (53,54). Following these investigations, the aim of the present study was to identify cancer stem-like cells in primary human lung cancer cells obtained from surgical specimens and to assess the differences and similarities between adenocarcinoma (ADENO) and squamous (SQUAMO) cell carcinoma using a combination of ALDH and CD44.…”

IL-6 Impairs the Activity of Vitamin D3 in the Regulation of Epithelial-Mesenchymal Transition in Triple Negative Breast Cancer

“…Stemness involves the ability of cells to self-renew and differentiate into multiple lineages (Wu and Izpisua Belmonte, 2016). Although these properties are displayed by adult stem cells to maintain tissue homeostasis, Cancer Stem Cells (CSCs), a small population of cells within tumors holding stemness properties, are responsible for tumor recurrence, metastasis, and drug resistance (Aponte and Caicedo, 2017). A transmembrane glycoprotein, CD44, has been recognized as one of the key markers for stemness in breast cancer (Shima et al, 2017).…”