Cancer stem cells (CSCs), cervical CSCs and targeted therapies

Abstract

Accumulating evidence has shown that cancer stem cells (CSCs) have a tumour-initiating capacity and play crucial roles in tumour metastasis, relapse and chemo/radio-resistance. As tumour propagation initiators, CSCs are considered to be promising targets for obtaining a better therapeutic outcome. Cervical carcinoma is the most common gynaecological malignancy and has a high cancer mortality rate among females. As a result, the investigation of cervical cancer stem cells (CCSCs) is of great value. However, the numbers of cancer cells and corresponding CSCs in malignancy are dynamically balanced, and CSCs may reside in the CSC niche, about which little is known to date. Therefore, due to their complicated molecular phenotypes and biological behaviours, it remains challenging to obtain “purified” CSCs and continuously culture CSCs for further in vitro studies without the cells losing their stem properties. At present, CSC-related markers and functional assays are used to purify, identify and therapeutically target CSCs both in vitro and in vivo. Nevertheless, CSC-related markers are not universal to all tumour types, although some markers may be valid in multiple tumour types. Additionally, functional identifications based on CSC-specific properties are usually limited in in vivo studies. Furthermore, an optimal method for identifying potential CCSCs in CCSC studies has not been previously published, and these techniques are currently of great importance. This article updates our knowledge on CSCs and CCSCs, reviews potential stem cell markers and functional assays for identifying CCSCs, and describes the potential of targeting CCSCs in the treatment of cervical carcinoma.

OGT-mediated O-GlcNAcylation on GLDC promotes metastasis in cervical cancer

“…Moreover, our data show that this increased expression markedly promoted migration of cervical cancer cells, suggesting that GLDC is involved in metastasis promotion. Since GLDC functioned in driving tumorigenesis in cancer stem cells (CSCs) [9], and CSCs is critical for tumor metastasis [34][35][36], GLDC might be the connection between CSCs and metastasis. In one hand, metastasis could be triggered by CSCs via elevated activities of glycine metabolism enzymes including GLDC.…”

Exosome-Based Cancer Therapy: Implication for Targeting Cancer Stem Cells

“…Cancer stem cells (CSCs) are a small subpopulation of immortal cancer cells, capable of long-term self-renewal, and differentiation into heterogeneous cancer cell lineages (Bandhavkar, 2016). Although the existing of CSCs is still controversial, recently a number of studies have identified CSCs in several types of solid tumor, such as renal cancer, breast cancer, lung cancer, liver cancer, prostate cancer, melanoma, and in leukemia (Huang and Rofstad, 2016). CSCs are known as the source of primary and metastatic cancer, and the root of chemo- and radio-therapy resistance (Sales et al, 2007; Colak and Medema, 2014).…”

“…In addition to targeting cell surface markers, exosomes can also target CSC specific signal pathways. For example, Wnt, Notch, Hippo, Hedgehog, NF-κB, and TGF-β pathways are crucial to maintain the CSC capacities such as self-renewal, differentiation, tumor initiation, and drug resistance (Dandawate et al, 2016; Huang and Rofstad, 2016; Rinkenbaugh and Baldwin, 2016). Using exosomes loaded with inhibitors, miRNAs, or siRNAs to target these pathways can be considered an alternative way to achieve CSC targeting.…”

Impact of modulation of telomerase and cancer stem‐cell marker OCT4 axis in cervical cancer pathogenesis with underlying HPV16 infection

“…The HPV oncoprotein E6 has been demonstrated to participate in maintenance of stem‐cell phenotype and stemness in cervical cancer cells . Multiple stem‐cell specific markers and functional assays have been used to identify putative CSCs for both in vitro and in vivo studies . Notably it is believe that the aberrant expression of certain stem‐cell‐related nuclear transcription factors, such as octamer‐binding transcription factor 4 (OCT4), SOX2, and NANOG, could contribute to cervical carcinogenesis.…”