scholarly journals Expression Patterns of Cancer-Testis Antigens in Human Embryonic Stem Cells and Their Cell Derivatives Indicate Lineage Tracks

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Nadya Lifantseva ◽  
Anna Koltsova ◽  
Tatyana Krylova ◽  
Tatyana Yakovleva ◽  
Galina Poljanskaya ◽  
...  

Pluripotent stem cells can differentiate into various lineages but undergo genetic and epigenetic changes during long-term cultivation and, therefore, require regular monitoring. The expression patterns of cancer-testis antigens (CTAs) MAGE-A2, -A3, -A4, -A6, -A8, -B2, and GAGE were examined in undifferentiated human embryonic stem (hES) cells, their differentiated derivatives, teratocarcinoma (hEC) cells, and cancer cell lines of neuroectodermal and mesodermal origin. Undifferentiated hES cells and embryoid body cells expressed MAGE-A3, -A6, -A4, -A8, and GAGEs while later differentiated derivatives expressed only MAGE-A8 or MAGE-A4. Likewise, mouse pluripotent stem cells also express CTAs of Magea but not Mageb family. Despite similarity of the hES and hEC cell expression patterns, MAGE-A2 and MAGE-B2 were detected only in hEC cells but not in hES cells. Moreover, our analysis has shown that CTAs are aberrantly expressed in cancer cell lines and display low tissue specificity. The identification of CTA expression patterns in pluripotent stem cells and their derivatives may be useful for isolation of abnormally CTA-expressing cells to improve the safety of stem-cell based therapy.

2014 ◽  
Vol 3 (5) ◽  
pp. 1099-1111 ◽  
Author(s):  
Blanca D. Lopez‐Ayllon ◽  
Veronica Moncho‐Amor ◽  
Ander Abarrategi ◽  
Inmaculada Ibañez Cáceres ◽  
Javier Castro‐Carpeño ◽  
...  

2014 ◽  
Vol 41 (9) ◽  
pp. 5877-5881 ◽  
Author(s):  
Sercan Ergun ◽  
Kaifee Arman ◽  
Ebru Temiz ◽  
İbrahim Bozgeyik ◽  
Önder Yumrutaş ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jeong Yoon Han ◽  
Yu Kyeong Han ◽  
Ga-Young Park ◽  
Sung Dae Kim ◽  
Chang Geun Lee

2012 ◽  
Vol 24 (1) ◽  
pp. 220
Author(s):  
B. P. Telugu ◽  
T. Ezashi ◽  
A. Alexenko ◽  
S. Lee ◽  
R. S. Prather ◽  
...  

Authentic embryonic stem cells (ESC) may never have been successfully derived from the inner cell mass (ICM) of pig and other ungulates, despite over 25 years of effort. Recently, porcine induced pluripotent stem cells (piPSC) were generated by reprogramming somatic cells with a combination of four factors OCT4, SOX2, KLF4 and c-MYC (OSKM) delivered by lentiviral transduction. The established piPSC are analogous to FGF2-dependent human (h) ESC and murine “epiblast stem cells,” and are likely to advance swine as a model in biomedical research. Here, we report for the first time, the establishment of LIF-dependent, so called naïve type pluripotent stem cells (1) from the inner cell mass (ICM) of porcine blastocysts by up-regulating the expression of KLF4 and POU5F1; and (2) from umbilical cord mesenchyme (Wharton's jelly) by transduction with OSKM factors and subsequent culture in the presence of LIF-based medium with inhibitors that substitute for low endogenous expression of c-MYC and KLF4 and promote pluripotency. The 2 compounds that have been used in this study are, CHIR99021 (CH), which substitutes c-MYC by inhibiting GSK3B and activating WNT signalling and Kenpaullone (KP), which inhibits both GSK3B and CDK1 and supplants KLF4 function. The lentiviral vectors employed for introducing the re-programming genes were modified for doxycycline-mediated induction of expression (tet-on) and are ‘floxed’ for Cre-mediated recombination and removal of transgenes following complete reprogramming. Two LIF-dependent cell lines have been derived from the ICM cells of late d 5.5 in vitro produced blastocysts and four from umbilical cord mesenchyme recovered from fetuses at d 35 of pregnancy. The derived stem cell lines are alkaline phosphatase-positive, resemble mouse embryonic stem cells in colony morphology, cell cycle interval, transcriptome profile and expression of pluripotent markers, such as POU5F1, SOX2 and surface marker SSEA1. They are dependent on LIF signalling for maintenance of pluripotency, can be cultured over extended passage (>50) with no senescence. Of importance, the ICM-derived lines have been successful in their ability to form teratomas. The cells could be cultured in feeder free conditions on a synthetic matrix in the presence of chemically defined medium and can be coaxed to differentiate under xeno-free conditions. Currently, the piPSC lines are being investigated for their ability to give rise to teratomas and to produce a live offspring by nuclear transfer. Supported by Addgene Innovation Award, MO Life Sciences Board Grant 00022147 and NIH grant HD21896.


2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Oleg Shuvalov ◽  
Alyona Kizenko ◽  
Alexey Petukhov ◽  
Olga Fedorova ◽  
Alexandra Daks ◽  
...  

AbstractSEMG1 and SEMG2 genes belong to the family of cancer-testis antigens (CTAs), whose expression normally is restricted to male germ cells but is often restored in various malignancies. High levels of SEMG1 and SEMG2 expression are detected in prostate, renal, and lung cancer as well as hemoblastosis. However, the functional importance of both SEMGs proteins in human neoplasms is still largely unknown. In this study, by using a combination of the bioinformatics and various cellular and molecular assays, we have demonstrated that SEMG1 and SEMG2 are frequently expressed in lung cancer clinical samples and cancer cell lines of different origins and are negatively associated with the survival rate of cancer patients. Using the pull-down assay followed by LC-MS/MS mass-spectrometry, we have identified 119 proteins associated with SEMG1 and SEMG2. Among the SEMGs interacting proteins we noticed two critical glycolytic enzymes-pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). Importantly, we showed that SEMGs increased the protein level and activity of both PKM2 and LDHA. Further, both SEMGs increased the membrane mitochondrial potential (MMP), glycolysis, respiration, and ROS production in several cancer cell lines. Taken together, these data provide first evidence that SEMGs can up-regulate the energy metabolism of cancer cells, exemplifying their oncogenic features.


2007 ◽  
Vol 29 (6) ◽  
pp. 467-476
Author(s):  
Joana Paredes ◽  
Ana Luísa Correia ◽  
Ana Sofia Ribeiro ◽  
Fernando Schmitt

Background: P120-catenin is a member of the Armadillo protein family, which is involved in intercellular adhesion and cell signalling. It directly interacts with the classical cadherins juxtamembrane domain and contributes for both junction formation and its disassembly. Accumulating evidences indicate that p120-catenin is important in tumour formation and progression, although the role of their multiple spliced isoforms in the regulation of cadherin-mediated adhesion of malignant cells is still not well understood. We investigated the expression of p120-catenin isoforms in a collection of breast cancer cell lines with distinct molecular profiles and expressing different cadherins. Methods: We assessed the expression by RT-PCR and Western-blotting analysis. Results: We observed that the expression of p120-catenin isoforms was associated with the genomic and transcriptional phenotype of breast cancer cells. Besides, the recruitment of p120-catenin isoforms was not apparently related with the particular expression of E-, P- or N-cadherin. Conclusion: We demonstrate that mammary tumour cells exhibit a characteristic p120-catenin isoform expression profile, depending from their specific genomic and transcriptional properties. These particular expression patterns, combined with other regulatory proteins and in a specific cellular context, may explain how p120-catenin can either contribute to strength intercellular adhesions or instead to promote cell motility.


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