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The International Journal of... Mar 1993Germ cell tumors of the testis and the ovary have been studied extensively in humans and experimental animals. Murine teratocarcinomas proved to be one of the best... (Review)
Review
Germ cell tumors of the testis and the ovary have been studied extensively in humans and experimental animals. Murine teratocarcinomas proved to be one of the best experimental models for elucidating the histogenesis of these tumors and the nature of their undifferentiated stem cells. These spontaneous and experimentally induced tumors, especially those produced from early postimplantation stage embryos, provided a wealth of data about the differentiation of tumor stem cells and the regulation of their growth. This made it possible to draw parallels between the teratocarcinoma cells and their normal equivalents in the embryo. Cumulative data indicate that neoplastic development of murine embryonic cells is just one of the possible ontogenic pathways these cells can take while proliferating in various developmental fields. The malignancy of teratocarcinoma stem cells is determined genetically but can be regulated epigenetically. Development of stem cells in murine teratocarcinomas parallels events in the normal embryo, suggesting that events in the tumor have their normal regulatory counterparts in the embryo proper. The study of early embryos has provided data relevant for oncology, while the study of murine teratocarcinoma helped elucidate some basic developmental events occurring normally in the embryo.
Topics: Animals; Cell Differentiation; Embryo, Mammalian; Embryonal Carcinoma Stem Cells; Female; Humans; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Neoplastic Stem Cells; Teratoma
PubMed: 8507568
DOI: No ID Found -
Oncotarget May 2019The biological roles of cancer-testis antigens of the Melanoma antigen (Mage) family in mammalian development, stem cell differentiation and carcinogenesis are largely...
The biological roles of cancer-testis antigens of the Melanoma antigen (Mage) family in mammalian development, stem cell differentiation and carcinogenesis are largely unknown. In order to understand the involvement of the family genes in maintenance of normal and cancer stem cells, the expression patterns of and gene subfamilies were analyzed during the self-renewal and differentiation of mouse pluripotent stem and teratocarcinoma cells. Clustering analysis based on the gene expression profiles of undifferentiated and differentiating cell populations revealed strong correlations between expression patterns and differentiation and malignant states. Gene co-expression analysis disclosed the potential contributions of family members in self-renewal and differentiation of pluripotent stem and teratocarcinoma cells. Two gene clusters including and were identified as functional antagonists with opposing roles in the regulation of proliferation and differentiation of mouse pluripotent stem and teratocarcinoma cells. The identified aberrant expression patterns of and in teratocarcinoma cells can be considered as specific teratocarcinoma biomarkers promoted the malignant phenotype. Our study first provides a model for the involvement of family members in regulatory networks during the self-renewal and early differentiation of normal and cancerous stem cells for further research of the predicted functional modules and the development of new cancer treatment strategies.
PubMed: 31143371
DOI: 10.18632/oncotarget.26933 -
Stem Cells Translational Medicine Aug 2022Human pluripotent stem cells (hPSCs) are currently evaluated for clinical applications due to their proliferation and differentiation capacities, raising the need to...
Human pluripotent stem cells (hPSCs) are currently evaluated for clinical applications due to their proliferation and differentiation capacities, raising the need to both assess and enhance, the safety of hPSC-based treatments. Distinct molecular features contribute to the tumorigenicity of hPSCs, manifested in the formation of teratoma tumors upon transplantation in vivo. Prolonged in vitro culturing of hPSCs can enhance selection for specific genetic aberrations, either at the chromosome or gene level. Some of these aberrations are tightly linked to human tumor pathology and increase the tumorigenic aggressiveness of the abnormal cells. In this perspective, we describe major tumor-associated risk factors entailed in hPSC-based therapy, and present precautionary and safety measures relevant for the development and application of such therapies.
Topics: Carcinogenesis; Cell Differentiation; Humans; Pluripotent Stem Cells; Teratoma
PubMed: 35679163
DOI: 10.1093/stcltm/szac039 -
Frontiers in Neurology 2012Primary central nervous system (CNS) teratomas are rare tumors that consist of all three germ cell layers. We describe a young man with a primary malignant CNS...
Primary central nervous system (CNS) teratomas are rare tumors that consist of all three germ cell layers. We describe a young man with a primary malignant CNS teratocarcinoma presenting as leptomeningeal carcinomatosis. Diagnosis of primary CNS teratocarcinomas is challenging; relentless pursuit of the diagnosis must follow even if early ancillary studies are inconclusive.
PubMed: 22363315
DOI: 10.3389/fneur.2012.00014 -
Human Reproduction Update 2011Pluripotent stem cells have been derived from a variety of sources such as from the inner cell mass of preimplantation embryos, from primordial germ cells, from... (Review)
Review
BACKGROUND
Pluripotent stem cells have been derived from a variety of sources such as from the inner cell mass of preimplantation embryos, from primordial germ cells, from teratocarcinomas and from male germ cells. The recent development of induced pluripotent stem cells demonstrates that somatic cells can be reprogrammed to a pluripotent state in vitro.
METHODS
This review summarizes our current understanding of the origins of mouse and human pluripotent cells. We pay specific attention to transcriptional and epigenetic regulation in pluripotent cells and germ cells. Furthermore, we discuss developmental aspects in the germline that seem to be of importance for the transition of germ cells towards pluripotency. This review is based on literature from the Pubmed database, using Boolean search statements with relevant keywords on the subject.
RESULTS
There are distinct molecular mechanisms involved in the generation and maintenance of the various pluripotent cell types. Furthermore, there are important similarities and differences between the different categories of pluripotent cells in terms of phenotype and epigenetic modifications. Pluripotent cell lines from various origins differ in growth characteristics, developmental potential, transcriptional activity and epigenetic regulation. Upon derivation, pluripotent stem cells generally acquire new properties, but they often also retain a 'footprint' of their tissue of origin.
CONCLUSIONS
In order to further our knowledge of the mechanisms underlying self-renewal and pluripotency, a thorough comparison between different pluripotent stem cell types is required. This will progress the use of stem cells in basic biology, drug discovery and future clinical applications.
Topics: Animals; Blastocyst Inner Cell Mass; Cell Differentiation; Cell Line; Cell Lineage; Chromatin Assembly and Disassembly; Embryonic Development; Embryonic Stem Cells; Epigenesis, Genetic; Female; Gene Expression Regulation; Humans; Male; Mice; Phenotype; Pluripotent Stem Cells; Rats
PubMed: 20705693
DOI: 10.1093/humupd/dmq035 -
Bioorganic & Medicinal Chemistry May 2018LSD1/KDM1 is a histone demethylase that preferentially removes methyl groups from the mono- and di-methylated lysine 4 in histone H3 (H3K4), key marks for active...
LSD1/KDM1 is a histone demethylase that preferentially removes methyl groups from the mono- and di-methylated lysine 4 in histone H3 (H3K4), key marks for active chromatin for transcriptional activation. LSD1 is essential for pluripotent embryonic stem cells and embryonic teratocarcinoma/carcinoma cells and its expression is often elevated in various cancers. We developed a new LSD1 inhibitor, CBB3001, which potently inhibited LSD1 activity both in vitro and in vivo. CBB3001 also selectively inhibited the growth of human ovarian teratocarcinoma PA-1 and mouse embryonic carcinoma F9 cells, caused the downregulation of pluripotent stem cell proteins SOX2 and OCT4. However, CBB3001 does not have significant inhibition on the growth of human colorectal carcinoma HCT116 cells or mouse fibroblast NIH3T3 cells that do not express these stem cell proteins. Our studies strongly indicate that CBB3001 is a specific LSD1 inhibitor that selectively inhibits teratocarcinoma and embryonic carcinoma cells that express SOX2 and OCT4.
Topics: Animals; Antineoplastic Agents; Carcinoma, Embryonal; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzyme Inhibitors; HCT116 Cells; Histone Demethylases; Humans; Mice; Molecular Structure; NIH 3T3 Cells; Structure-Activity Relationship; Teratocarcinoma
PubMed: 29439916
DOI: 10.1016/j.bmc.2018.01.031 -
The American Journal of Pathology Jun 2010In each major theory of the origin of cancer-field theory, chemical carcinogenesis, infection, mutation, or epigenetic change-the tissue stem cell is involved in the... (Review)
Review
In each major theory of the origin of cancer-field theory, chemical carcinogenesis, infection, mutation, or epigenetic change-the tissue stem cell is involved in the generation of cancer. Although the cancer type is identified by the more highly differentiated cells in the cancer cell lineage or hierarchy (transit-amplifying cells), the property of malignancy and the molecular lesion of the cancer exist in the cancer stem cell. In the case of teratocarcinomas, normal germinal stem cells have the potential to become cancers if placed in an environment that allows expression of the cancer phenotype (field theory). In cancers due to chemically induced mutations, viral infections, somatic and inherited mutations, or epigenetic changes, the molecular lesion or infection usually first occurs in the tissue stem cells. Cancer stem cells then give rise to transit-amplifying cells and terminally differentiated cells, similar to what happens in normal tissue renewal. However, the major difference between cancer growth and normal tissue renewal is that whereas normal transit amplifying cells usually differentiate and die, at various levels of differentiation, the cancer transit-amplifying cells fail to differentiate normally and instead accumulate (ie, they undergo maturation arrest), resulting in cancer growth.
Topics: Animals; Cell Differentiation; Cell Lineage; Cell Transformation, Neoplastic; Epigenesis, Genetic; Humans; Neoplasms; Neoplastic Stem Cells; Stem Cell Niche; Stem Cells; Teratocarcinoma
PubMed: 20431026
DOI: 10.2353/ajpath.2010.091064 -
Stem Cell Research Jul 2009The use of cell surface antigens to characterise embryonic stem (ES) cells, and to monitor their differentiation, has had a long history, stretching back to the early... (Review)
Review
The use of cell surface antigens to characterise embryonic stem (ES) cells, and to monitor their differentiation, has had a long history, stretching back to the early studies of differentiation antigens in the haematopoietic system, and their application to teratocarcinomas and embryonal carcinoma (EC) cells in the laboratory mouse. A wide series of such antigens, which include both glycolipids and glycoproteins are now extensively used in studies of human ES cells. Many of these were first identified using both mouse and human EC cells, although the cell surface antigen phenotype of human EC and ES cells has proved to be significantly different from that of murine EC and ES cells.
Topics: Animals; Antigens, Surface; Antigens, Tumor-Associated, Carbohydrate; Cell Differentiation; Embryonal Carcinoma Stem Cells; Glycolipids; Humans; Lewis X Antigen; Proteoglycans; Stage-Specific Embryonic Antigens
PubMed: 19398226
DOI: 10.1016/j.scr.2009.04.001 -
Philosophical Transactions of the Royal... Apr 2002The recent derivation of human embryonic stem (ES) cell lines, together with results suggesting an unexpected degree of plasticity in later, seemingly more restricted,... (Review)
Review
The recent derivation of human embryonic stem (ES) cell lines, together with results suggesting an unexpected degree of plasticity in later, seemingly more restricted, stem cells (so-called adult stem cells), have combined to focus attention on new opportunities for regenerative medicine, as well as for understanding basic aspects of embryonic development and diseases such as cancer. Many of the ideas that are now discussed have a long history and much has been underpinned by the earlier studies of teratocarcinomas, and their embryonal carcinoma (EC) stem cells, which present a malignant surrogate for the normal stem cells of the early embryo. Nevertheless, although the potential of EC and ES cells to differentiate into a wide range of tissues is now well attested, little is understood of the key regulatory mechanisms that control their differentiation. Apart from the intrinsic biological interest in elucidating these mechanisms, a clear understanding of the molecular process involved will be essential if the clinical potential of these cells is to be realized. The recent observations of stem-cell plasticity suggest that perhaps our current concepts about the operation of cell regulatory pathways are inadequate, and that new approaches for analysing complex regulatory networks will be essential.
Topics: Animals; Cell Differentiation; Cell Line; Cell Transformation, Neoplastic; Embryo, Mammalian; Humans; Stem Cells; Teratocarcinoma
PubMed: 12028783
DOI: 10.1098/rstb.2002.1058 -
Cell Regeneration (London, England) 2012Pluripotency is depicted by a self-renewing state that can competently differentiate to form the three germ layers. Different stages of early murine development can be... (Review)
Review
Pluripotency is depicted by a self-renewing state that can competently differentiate to form the three germ layers. Different stages of early murine development can be captured on a petri dish, delineating a spectrum of pluripotent states, ranging from embryonic stem cells, embryonic germ cells to epiblast stem cells. Anomalous cell populations displaying signs of pluripotency have also been uncovered, from the isolation of embryonic carcinoma cells to the derivation of induced pluripotent stem cells. Gaining insight into the molecular circuitry within these cell types enlightens us about the significance and contribution of each stage, hence deepening our understanding of vertebrate development. In this review, we aim to describe experimental milestones that led to the understanding of embryonic development and the conception of pluripotency. We also discuss attempts at exploring the realm of pluripotency with the identification of pluripotent stem cells within mouse teratocarcinomas and embryos, and the generation of pluripotent cells through nuclear reprogramming. In conclusion, we illustrate pluripotent cells derived from other organisms, including human derivatives, and describe current paradigms in the comprehension of human pluripotency.
PubMed: 25408870
DOI: 10.1186/2045-9769-1-7