Hybrids of pluripotent and nullipotent human embryonal carcinoma cells: Partial retention of a pluripotent phenotype

Durán, Cristina; Talley, Polly; Walsh, James; Pigott, C. D.; Morton, I E; Andrews, Peter W.

doi:10.1002/ijc.1355

Cited by 30 publications

(18 citation statements)

References 48 publications

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“…These observations on an established human EC line are in line with previous reports of osteogenic characteristics in mouse EC-derived lines [Poliard et al, 1993;Shukunami et al, 1997]. The differentiation ability of existing human EC lines is heterogeneous [Pera et al, 1989;Duran et al, 2001]. NTera2 cells originate from a human testicular EC and have been well characterized, including their propensity to form neuroectodermal lineages in response to retinoic acid [Andrews et al, 1984;Andrews, 2002].…”

Section: Discussionsupporting

confidence: 78%

“…Injections into mouse models indicate that human EC lines can form tumours containing a broad range of tissues, occasionally including cartilage [Pera et al, 1989;Andrews, 2002]. However, this differentiation has not been widely reported for NTera2 [Duran et al, 2001], and so far, reports describing their in vitro potential suggest a limited range of mesodermal cell types in NTera2 cultures [Chadalavada et al, 2005;Pal and Ravindran, 2006;Simoes and Ramos, 2007]. Our study provides new evidence that NTera2 cultures can deposit minerals in vitro after OM treatment.…”

Section: Discussionmentioning

confidence: 72%

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Differences in the Pattern and Regulation of Mineral Deposition in Human Cell Lines of Osteogenic and Non-Osteogenic Origin

Rashidi

Strohbuecker²,

Jackson³

et al. 2011

Cells Tissues Organs

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Bone marrow-derived mesenchymal stem cells (MSCs) are widely used as a cellular model of bone formation, and can mineralize in vitro in response to osteogenic medium (OM). It is unclear, however, whether this property is specific to cells of mesenchymal origin. We analysed the OM response in 3 non-osteogenic lines, HEK293, HeLa and NTera, compared to MSCs. Whereas HEK293 cells failed to respond to OM conditions, the 2 carcinoma-derived lines NTera and HeLa deposited a calcium phosphate mineral comparable to that present in MSC cultures. However, unlike MSCs, HeLa and NTera cultures did so in the absence of dexamethasone. This discrepancy was confirmed, as bone morphogenetic protein inhibition obliterated the OM response in MSCs but not in HeLa or NTera, indicating that these 2 models can deposit mineral through a mechanism independent of established dexamethasone or bone morphogenetic protein signalling.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 72%

Differences in the Pattern and Regulation of Mineral Deposition in Human Cell Lines of Osteogenic and Non-Osteogenic Origin

Rashidi

Strohbuecker²,

Jackson³

et al. 2011

Cells Tissues Organs

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“…Fielding et al (57) reported that cholesterol and other sterols have the ability to alter caveolin-1 mRNA levels. Therefore, to ensure that the contents of our high serum media did not cause caveolin-1 expression to be altered independent of the differentiation process, we employed a control cell line, 2102Ep, which is a human embryonic carcinoma cell line that is unable to differentiate (35,58) and thereby also does not undergo EMT. After receiving identical stimulation as the NT2/D1 cells, indeed, no morphological changes occurred in these cells.…”

Section: Stimulated Nt2/d1 and Nmumg Cells Both Undergo Emt-mentioning

confidence: 99%

“…Further, we wanted to determine the impact of caveolin-1 on aspects of cancer cell adhesion, because of the implicated role of caveolin in cell motility (18,19,34). The pluripotent human embryonic carcinoma cell line NT2/D1 has the potential to differentiate into a variety of cell types upon appropriate stimulation (35)(36)(37) and can accordingly undergo EMT. It is well documented that the mouse mammary epithelial cells NMuMG undergo EMT upon treatment with TGF-␤1 (38).…”

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confidence: 99%

Caveolin-1 Up-regulation during Epithelial to Mesenchymal Transition Is Mediated by Focal Adhesion Kinase

Bailey

2008

Journal of Biological Chemistry

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Emerging evidence has shown that caveolin-1 is up-regulated in a number of metastatic cancers and can influence various aspects of cell migration. However, in general, the role of caveolin-1 in cancer progression is poorly understood. In the present study, we examined alterations in caveolin-1 expression during epithelial-to-mesenchymal transition (EMT) and the ability of caveolin-1 to alter cancer cell adhesion, an aspect of cell motility. We employed two EMT cell models, the human embryonic carcinoma cell line NT2/D1, and TGF-␤1-treated NMuMG cells, which are derived from normal mouse mammary epithelia. Caveolin-1 expression was substantially upregulated in both cell lines following the induction of EMT and was preceded by increased activation of focal adhesion kinase (FAK) and Src, two known tyrosine kinases involved in EMT. We hypothesized that caveolin-1 expression could be influenced by increased FAK phosphorylation, to which Src is a known contributor. Caveolin-1 (Cav-1), 2 the principal structural protein of the cholesterol-rich plasma membrane invaginations known as caveolae (1), was first discovered as a Src substrate in Rous sarcoma virus-transformed cells (2, 3), and appears to play opposing roles in the context of cancer (4). Studies have labeled it both as a tumor suppressor (5-7) and an oncogene (8 -12). Support for the tumor suppressor theory includes the fact that caveolin-1 is known to sequester and dampen the activity of a variety of signaling molecules that can cause cell transformation (13) and the localization of caveolin-1 near a tumor suppressor locus on chromosome 7 (14). Clues that caveolin-1 may be serving a tumor promoter effect first arose with the observation that prostate cancer tissue expresses more caveolin-1 than does normal tissue (15). The list has since expanded and includes esophageal squamous cell carcinoma, multiple myeloma, Ewing's sarcoma family tumors, clear cell renal carcinoma, urinary bladder tumors, and non-small cell lung cancer (4,8,16,17). This suppressor/promoter discrepancy could be due to the examination of various cell types, cancer stages, variations in in vitro versus in vivo data, or an indicator that caveolin can serve different roles depending on the context in which its function is being examined. One trend that has more recently arisen, however, is that caveolin-1 is up-regulated in a number of metastatic cancers including prostate and lung, and consistent with this, we and others (18 -21) have shown that caveolin-1 plays an important role in cell migration.Epithelial-to-mesenchymal transition (EMT) is a process that occurs during embryonic development (as stem cells differentiate into various components of the organism) (22) and during cancer progression (as tumor cells gradually acquire a more motile phenotype). Cancer cells that undergo EMT, which entails an intricate series of changes in cell-cell contacts (23), cell-matrix interactions, and cell signaling (24), can gain the ability to invade, extravasate, and potentially re-establish as a metastat...

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“…In another study, we had investigated the behaviour of hybrid cells produced by fusing a pluripotent human EC cells from the NTERA2 line with nullipotent human EC cells from the 2102Ep line (Duran et al, 2001). NTERA2, but not 2102Ep, EC cells differentiate in response to retinoic acid, producing neurons as well as a range of other cell types (Andrews, 1984;Andrews et al, 1982;Matthaei et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

The CDK inhibitor p27 enhances neural differentiation in pluripotent NTERA2 human EC cells, but does not permit differentiation of 2102Ep nullipotent human EC cells

Bahrami

Matin

Andrews

2005

Mechanisms of Development

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Embryonal carcinoma (EC) cells, the stem cells of teratocarcinomas, are the malignant counterparts of pluripotent embryonic stem (ES) cells, but commonly exhibit a reduced ability to differentiate, presumably because of continual selection for genetic changes that alter the balance between self-renewal, differentiation and apoptosis in favour of self-renewal. To explore the nature of the genetic changes that promote nullipotency, we have compared two human EC cell lines, a 'nullipotent' line, 2102Ep, and a 'pluripotent' line, NTERA2. A hybrid derived by fusion of these cells differentiates in response to retinoic acid but, unlike the parental NTERA2 line, does not form terminally differentiated neurons. This implies that the nullipotent EC cell line, 2102Ep, differs in expression of at least two functions in comparison with the NTERA2 pluripotent line, one affecting commitment to differentiation, and one affecting terminal neural differentiation. We have now investigated the possible role of the CDK inhibitor, p27kip1 (p27) in commitment and terminal differentiation. In NTERA2, but not in 2102Ep cells, retinoic acid induces up-regulation of p27 expression, suggesting that 2102Ep cells lack this capacity. However, constitutive expression of a p27 transgene does not overcome the block to differentiation in the 2102Ep parental cells; commitment to differentiation must be blocked elsewhere. On the other hand, constitutive over-expression of p27 from a transgene enhances the neural differentiation of NTERA2 cells. Our results suggest that p27 plays a role in terminal neuronal differentiation of human EC cells, but not in their initial commitment to differentiation, and that other factors, possibly Cyclin D2, specifically limit its ability to promote neural differentiation.

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Hybrids of pluripotent and nullipotent human embryonal carcinoma cells: Partial retention of a pluripotent phenotype

Cited by 30 publications

References 48 publications

Differences in the Pattern and Regulation of Mineral Deposition in Human Cell Lines of Osteogenic and Non-Osteogenic Origin

Differences in the Pattern and Regulation of Mineral Deposition in Human Cell Lines of Osteogenic and Non-Osteogenic Origin

Caveolin-1 Up-regulation during Epithelial to Mesenchymal Transition Is Mediated by Focal Adhesion Kinase

The CDK inhibitor p27 enhances neural differentiation in pluripotent NTERA2 human EC cells, but does not permit differentiation of 2102Ep nullipotent human EC cells

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