The Mechanisms Behind Tumour Repopulation
Loredana G. Marcu, Iuliana Toma-Dasu, Alexandru Dasu, Claes Mercke in Radiotherapy and Clinical Radiobiology of Head and Neck Cancer, 2018
Other CSC markers trialed in HNC are CD133, ALDH1 and ABCG2 (Clay et al. 2010; Chen et al. 2011; Yanamoto et al. 2014). CD133 is a glycoprotein first identified as a hematopoietic stem cell marker; later, it was being investigated as a surface marker in several solid cancers, including head and neck (Chen et al. 2011). While the molecular mechanisms mediated by this marker in regulating CSCs are not fully elucidated, it was shown that overexpression of CD133 in HNC is negatively correlated with survival and, moreover, it serves as an indicator of tumour repopulation and malignant progression (Chen et al. 2011). Cells that express the intracellular enzyme aldehyde dehydrogenase (ALDH) were found to be a subset of the CD44+ cells, given that cells exhibiting increased levels of ALDH were identified to also have elevated CD44 expression (Clay et al. 2010). A study that was investigating the tumorigenic ability of cells expressing high levels of ALDH in HNC concluded that the activity of ALDH on its own is a highly selective marker for CSCs (Clay et al. 2010). In vivo head and neck studies showed that ALDH+ cells comprise a population that preserves its tumorigenic abilities after irradiation and could trigger tumour regrowth (Kurth et al. 2015). The same study indicated that ALDH activity in HNC is mainly attributed to the ALDH1A3 isoform, given that the inhibition of ALDH1A3 expression led to reduced tumour radioresistance (Kurth et al. 2015).
Targeted Therapy for Cancer Stem Cells
Surinder K. Batra, Moorthy P. Ponnusamy in Gene Regulation and Therapeutics for Cancer, 2021
CD44 like CD133 is a transmembrane glycoprotein that facilitates cell-cell and cell to ECM interactions and is found to be overexpressed in several cancers. Study on patient-derived AML blasts has revealed that treatment with anti-human CD44 monoclonal antibody to stimulate myeloid differentiation alters stem cell fate, and impedes homing to the microenvironment niche [81]. Doxorubicin and cyclophosphamide, in combination with anti-human CD44 antibody, have shown synergistic anti-cancerous activity in breast cancer and prevent relapse of aggressive breast cancer [82]. Another study by Tang et al. [83] used a mouse IgG1 anti-human CD44 receptor antibody on MiaPaCa-2 cells and was shown to inhibit CSCs tumorsphere formation, also decreasing tumor growth, metastasis and recurrence in pancreatic cancer xenografted nude mice.
Angiogenesis in Hematological Malignancies
Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey in Innovative Leukemia and Lymphoma Therapy, 2019
Vasculature of tumors is predominantly formed by angiogenesis, but can also be developed by postnatal vasculogenesis: the formation of new blood vessels from EPCs that differentiate into mature ECs (55). These EPCs are defined as CD34+/CD133+/CD177+/KDR+ cells, which originate in the bone marrow. EPC recruitment and mobilization have been positively correlated with an increase in VEGFA levels; in response to increased VEGFA levels at the site of the tumor, an increase in circulating EPCs was seen (Fig. 2) (56–58). Moreover, CD133+ cells differentiate into mature-type adherent ECs and abolish the CD133 expression in response to VEGFA (59). While it has been shown that these bone marrow–derived EPCs contribute to the tumor vessel formation by incorporating into the endothelium (60), a second group of proangiogenic cells was described; this population, rather than the EPCs, was thought to home in specifically to the tumor and was characterized by the expression of CD45+, TEK+, CD31−, and CD11b+ (61). Inhibition of those cells resulted in a significant reduction of tumor angiogenesis and growth. Finally, the existence of a third proangiogenic population was suggested, which is characterized by CD34, CXCR4 and FLT1 expression and is implicated in the initiation and formation of metastases (62).
Role and molecular mechanism of stem cells in colorectal cancer initiation
Published in Journal of Drug Targeting, 2020
Meng-Yan Wang, Yu-Han Qiu, Mei-Lian Cai, Cong-Hui Zhang, Xiao-Wei Wang, Hong Liu, Yi- Chen, Wu-Li Zhao, Jing-Bo Liu, Rong-Guang Shao
CD133, also called Prominin-1, is encoded by a single gene located on chromosome 4 (4p15.33) in humans. CD133 is a protein with five transmembrane passes composed of 865 amino acids and with a molecular mass of 120 kDa [36]. It is expressed in various embryonic and adult epithelial cells, as well as in non-epithelial cells such as haematopoietic stem cells [37]. Scientists initially isolated and identified colorectal CSCs marked by CD133. Studies have shown that CD133+ colorectal tumour cells formed tumour masses in mice at approximately twice the rate of CD133- cells. Clinical statistics indicate that high levels of CD133 are often associated with poor prognosis in patients with colorectal cancer [38]. With advancements in experiments, it was gradually determined that CD133 is not a precise surface marker useful for identifying colorectal CSCs. In fact, scientists have found a series of new surface protein makers, such as EpCAM, but CD133 seems to be still regarded as a more accurate marker to identify colorectal CSCs [39].
CD133: beyond a cancer stem cell biomarker
Published in Journal of Drug Targeting, 2019
Amir Barzegar Behrooz, Amir Syahir, Syahida Ahmad
The precise physiological function of CD133 is not clear, but its ubiquitous presence indicates its importance. As discussed above, it is found in plasma membrane protrusions that contain cholesterol-rich membrane microdomains, and these protrusions are associated with the presence of prominosomes. Prominosomes are extracellular vesicles that are attached to the plasma membrane that contains prominin proteins and are often thought of as being organisers of the plasma membrane [4,35]. One of the most common uses for CD133 is in the identification and isolation of stem cells from body tissues, not only in normal cells such as brain [36], kidney [37], prostate [18], bone marrow [19], liver [6,20], sarcoma [20], pancreas [20] and skin [20] but also in cancer cells from brain [21], liver [11,20], pancreas [20], lung [20], skin [20], sarcoma [20], prostate [20,38], colon [36] and ovary [36]. In other words, CD133 is a biomarker that can be used to identify stem cells in both normal and cancerous tissues.
High expression of RFX4 is associated with tumor progression and poor prognosis in patients with glioblastoma
Published in International Journal of Neuroscience, 2021
Hang Yeon Jeong, Hyun-Jin Kim, Cheol-Eun Kim, Seongsoo Lee, Moon-Chang Choi, Sung-Hak Kim
We first analyzed the expression level of RFX family genes in GSCs cultured in NBE (serum-free DMEM/F12 media supplemented with basic FGF and EGF) and FBS using the data available on a publicly available dataset (GSE4536). It was reported that NBE cultured GSCs exhibit more robust tumorigenic potential, heterogenous morphology, and indefinite self-renewal ability compared to the serum-cultured GSCs [17]. Among the RFX family genes, the levels of RFX4 transcript decreased remarkably when cells were differentiated in presence of FBS (Figure 1(A,B)). Next, we examined the endogenous expression of RFX4 in the CD133 positive and negative tumor cells. CD133 is a cell surface marker used to differentiate glioma stem cells from tumor tissues [20]. CD133 negative tumor cells exhibited significantly decreased expression of RFX4 (Figure 1(C)). Furthermore, we validated the association of RFX4 with glioma stem cells using primary human GBM-derived GSCs. Consistent with these findings, RFX4 and stem cell markers (CD15 and CD133) were significantly downregulated, and the differentiation markers (GFAP and TUBB3) were significantly upregulated in GSC11 and GSC23 cells cultured in presence of FBS.
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