Complexity of cancer stem cells

Sugihara, Eiji; Saya, Hideyuki

doi:10.1002/ijc.27961

Cited by 113 publications

(99 citation statements)

References 82 publications

(172 reference statements)

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“…For this reason, glioblastomas almost always relapse, highlighting the need for more precisely targeted therapeutic approaches. A number of recent studies have demonstrated that tumors are composed of cells with functional heterogeneity that form a hierarchy, especially in the context of tumor initiation (3,4). Characterized by its heterogeneous tumor types (5)(6)(7)(8), glioblastoma is now also thought to be initiated and maintained by a subpopulation of tumor cells, called brain tumor stem cells or brain tumor-initiating cells (BTIC; refs.…”

Section: Introductionmentioning

confidence: 99%

MIF Maintains the Tumorigenic Capacity of Brain Tumor–Initiating Cells by Directly Inhibiting p53

et al. 2016

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Tumor-initiating cells thought to drive brain cancer are embedded in a complex heterogeneous histology. In this study, we isolated primary cells from 21 human brain tumor specimens to establish cell lines with high tumorigenic potential and to identify the molecules enabling this capability. The morphology, sphereforming ability upon expansion, and differentiation potential of all cell lines were indistinguishable in vitro. However, testing for tumorigenicity revealed two distinct cell types, brain tumorinitiating cells (BTIC) and non-BTIC. We found that macrophage migration inhibitory factor (MIF) was highly expressed in BTIC compared with non-BTIC. MIF bound directly to both wild-type and mutant p53 but regulated p53-dependent cell growth by different mechanisms, depending on glioma cell line and p53 status. MIF physically interacted with wild-type p53 in the nucleus and inhibited its transcription-dependent functions. In contrast, MIF bound to mutant p53 in the cytoplasm and abrogated transcription-independent induction of apoptosis. Furthermore, MIF knockdown inhibited BTIC-induced tumor formation in a mouse xenograft model, leading to increased overall survival. Collectively, our findings suggest that MIF regulates BTIC function through direct, intracellular inhibition of p53, shedding light on the molecular mechanisms underlying the tumorigenicity of certain malignant brain cells. Cancer Res; 76(9); 2813-23. Ó2016AACR.

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Section: Introductionmentioning

confidence: 99%

MIF Maintains the Tumorigenic Capacity of Brain Tumor–Initiating Cells by Directly Inhibiting p53

et al. 2016

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“…The concept of cancer stem cells was originally introduced in hematological malignancies and further extended to solid cancers such as breast cancer and brain tumors. (97) Cancer stem cells have been characterized by their self-renewal potential, multidirectional differentiation potential, and niche dependence, similar to other stem cells, in addition to their highly tumorigenic potential. Furthermore, cancer stem cells have been known for their resistance to conventional chemotherapy or radiotherapy; therefore, they may be an emerging target for drug development.…”

Section: Evaluation Of Oncology Drugs Based On New Conceptsmentioning

confidence: 99%

Report on the use of non‐clinical studies in the regulatory evaluation of oncology drugs

et al. 2016

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Non-clinical studies are necessary at each stage of the development of oncology drugs. Many experimental cancer models have been developed to investigate carcinogenesis, cancer progression, metastasis, and other aspects in cancer biology and these models turned out to be useful in the efficacy evaluation and the safety prediction of oncology drugs. While the diversity and the degree of engagement in genetic changes in the initiation of cancer cell growth and progression are widely accepted, it has become increasingly clear that the roles of host cells, tissue microenvironment, and the immune system also play important roles in cancer. Therefore, the methods used to develop oncology drugs should continuously be revised based on the advances in our understanding of cancer. In this review, we extensively summarize the effective use of those models, their advantages and disadvantages, ranges to be evaluated and limitations of the models currently used for the development and for the evaluation of oncology drugs.

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“…In additional, the cancer stem cell theory has been proposed [38,49,50] . Cancer stem cells (CSCs) are a subpopulation of tumor cells that have the capacity to self-renew, provide life-long cell growth and produce distinct cell clones [49][50][51] . The detailed analysis of properties and methods of isolation of CSCs has been presented in a series of reviews.…”

Section: Modern Biochemistry and Post-genomic Technologies In Researcmentioning

confidence: 99%

Modern Biochemistry in Research of Human Malignant Cells and Experimental Oncology

Шишкин

2016

Journal of Biochemistry and Molecular Biology Research

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characteristics and the gene expression patterns. Thus, the use of malignant cell lines ex vivo (as models of human cancers) is an important trend in search for key molecules of carcinogenesis in experimental oncology. EDITORIALThe biochemistry has a place of honor among the life sciences largely due to its fantastic success in 20 th century. Traditional biochemistry started with the study of chemical components of living organisms and their metabolism that provides life itself, and with description of the main types of biopolymers and other biomolecules. At that time technologies allowing to determine sequence of monomers in complex polymers such as nucleic acids and proteins (sequencing technologies) were designed. As a result, in the 80s of the 20 th century the entire human mitochondrial genome was identified, heavy and light mitochondrial DNA strands maps were constructed and their nucleotide sequences were determined [1,2] . Further similar studies were concerned with the complete genome sequencing of different bacteria and some eukaryotes [3][4][5] . In the last decade of 20 th century the DNA sequencing of the human nuclear genome was started that influenced the development of the life sciences [6][7][8] . To achieve the goal of determining the DNA sequence of the entire human genome the considerable resources of the international ABSTRACTModern biochemistry or biochemistry of 21th century is developing in many traditional fields: investigations of proteins, nucleic acids, lipids, carbohydrates, metabolites and metabolic processes, etc, however it has gained new features that based on success of Human Genome Project and on application of high performance technologies (post-genomic technologies). As a result, at the turn of the 21st century some new scientific disciplines, named "OMICS" (proteomics, transcriptomics, lipidomics, glycomics, metabolomics, etc) were created through advances in the biochemistry. Currently "OMICS" and post-genomic technologies are involved in mainstream of cancer research, including studies of human malignant cells. Since malignant tumors consist of heterogeneous cancer cells, the cultured cell lines have some advantages over biopsy simples for studies aimed at understanding the molecular basis of carcinogenesis. The malignant human cell lines differ considerably in their origin from tissues or organs, and therefore they vary widely in the differentiation EDITORIAL

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Complexity of cancer stem cells

Cited by 113 publications

References 82 publications

MIF Maintains the Tumorigenic Capacity of Brain Tumor–Initiating Cells by Directly Inhibiting p53

MIF Maintains the Tumorigenic Capacity of Brain Tumor–Initiating Cells by Directly Inhibiting p53

Report on the use of non‐clinical studies in the regulatory evaluation of oncology drugs

Modern Biochemistry in Research of Human Malignant Cells and Experimental Oncology

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