Teratocarcinomas and human embryology: Pluripotent human EC cell lines
Abstract
The histogenesis of germ cell tumours (GCT) reflects the normal processes of gametogenesis, fertilisation and subsequent embryonic cell differentiation. Understanding the mechanisms that control the differentiation of embryonal carcinoma (EC) cells into a variety of embryonic and extraembryonic cell types is pertinent to understanding the progression of GCT. EC cells also provide a tool for analysing the mechanisms that control differentiation during embryonic development, and particularly the mechanisms that control differentiation along alternative cell line, NTERA2, into neurones and other cell types in response to agents such as retinoic acid, HMBA and the bone morphogenetic proteins. We have also compared the pluripotent NTERA2 EC cells with other human EC cell lines that exhibit a much reduced capacity for cell differentiation. A variety of genes are activated during NTERA2 differentiation. In particular we have identified a novel human member of the wnt family. This wnt gene is activated following retinoic acid induction of differentiation but is later down-regulated as the cells mature into neurones and other cell types. We have also observed expression of genes belonging to the Frizzled family, which is likely to include genes encoding receptors for the wnt gene products. Thus in the NTERA2 system, genes pertinent to regulating cell differentiation during embryonic development are activated and appear to play a role in modulating how these pluripotent human EC cells…
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NTERA2 cells can locate and target glioma neoplasms in mouse models, particularly following retinoic acid treatment.
“NTERA2 teratocarcinoma cells closely resemble neural stem/progenitor cells, as they are capable of differentiating into glia and neurons, and of locating and targeting glioma neoplasms in mouse models, particularly following treatment with retinoic acid [45,46,47,48].”
From Optimized Wound Healing Assay to Study Extracellular Vesicle-Driven Glioblastoma Cell Migration (2026) · cites this paper as [45]
NTERA2 teratocarcinoma cells closely resemble neural stem/progenitor cells.
“NTERA2 teratocarcinoma cells closely resemble neural stem/progenitor cells, as they are capable of differentiating into glia and neurons, and of locating and targeting glioma neoplasms in mouse models, particularly following treatment with retinoic acid [45,46,47,48].”
From Optimized Wound Healing Assay to Study Extracellular Vesicle-Driven Glioblastoma Cell Migration (2026) · cites this paper as [45]
NTERA2 cells are capable of differentiating into glia and neurons.
“NTERA2 teratocarcinoma cells closely resemble neural stem/progenitor cells, as they are capable of differentiating into glia and neurons, and of locating and targeting glioma neoplasms in mouse models, particularly following treatment with retinoic acid [45,46,47,48].”
From Optimized Wound Healing Assay to Study Extracellular Vesicle-Driven Glioblastoma Cell Migration (2026) · cites this paper as [45]
An early phase of commitment to neuronal fate occurs within two days after RA-treatment for P19 and NT2/D1 cells; a later phase of terminal differentiation takes place between days five to eight in P19 cells and is delayed for more than three weeks in NT2/D1 cells.
“An early phase of commitment to neuronal fate occurs within two days after RA-treatment for P19 and NT2/D1 cells. A later phase of terminal differentiation takes place between days five to eight in P19 cells and is delayed for more than three weeks in NT2/D1 cells [42,43].”
From Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation (2004) · cites this paper as [43]
P19 and NT2/D1 have similar programs of neuronal differentiation, though the differentiation of P19 cells progresses more rapidly than that of NT2/D1 cells.
“P19 and NT2/D1 have similar programs of neuronal differentiation, though the differentiation of P19 cells progresses more rapidly than that of NT2/D1 cells [42,43].”
From Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation (2004) · cites this paper as [43]
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Sempere, L. F., Freemantle, S., Pitha-Rowe, I., Moss, E., Dmitrovsky, E., & Ambros, V. (2004) · Genome Biology · doi:10.1186/gb-2004-5-3-r13 · Cited by 1,578 · see citing works
Son, Y. S., Park, J. H., Kang, Y. K., Park, J., Choi, H. S., Lim, J. Y., Lee, J. E., Lee, J. B., Ko, M. S., Kim, Y., et al. (2005) · STEM CELLS · doi:10.1634/stemcells.2004-0307 · Cited by 54 · see citing works
Mantile, F., Kisovec, M., Adamo, G., Romancino, D. P., Hočevar, M., Božič, D., Bedina Zavec, A., Podobnik, M., Stoppelli, M. P., Kisslinger, A., et al. (2022) · Cancers · doi:10.3390/cancers14153700 · Cited by 18 · see citing works
Optimized Wound Healing Assay to Study Extracellular Vesicle-Driven Glioblastoma Cell Migration
D’Antonio, C., Mantile, F., Pocsfalvi, G., & Liguori, G. L. (2026) · Methods and Protocols · doi:10.3390/mps9030081
“NTERA2 teratocarcinoma cells closely resemble neural stem/progenitor cells, as they are capable of differentiating into glia and neurons, and of locating and targeting glioma neoplasms in mouse models, particularly following treatment with retinoic acid [45–48].”
Influential
- Authors
- ANDREWS, P. W.
- Affiliations
- University of Sheffield (GB)
- Corresponding author
- ANDREWS, PETER W.
- ORCID
- ANDREWS, PETER W.
- Venue
- APMIS
- Publisher
- Wiley
- Published
- 1998-01
- Volume
- 106
- Issue
- 1-6
- Pages
- 158-168
- ISSN
- 0903-4641 (ISSN-L)
- 1600-0463
- OpenAlex
- W2063948611
- Cited by
- 140
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 3 · 2013: 4 · 2012: 5
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Apmis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- teratocarcinoma, embryonal carcinoma, NTERA-2 cells, germ cell tumors, pluripotency, cell differentiation, neuronal differentiation, retinoic acid, hexamethylene bisacetamide, bone morphogenetic proteins, Frizzled receptors, embryonic development, histogenesis
- MeSH terms
- Cell Differentiation, Humans, Male, Stem Cells, Testicular Neoplasms, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Germinoma, Teratocarcinoma, Cell Lineage
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