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

Abstract

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.

ASXL3 Is a Novel Pluripotency Factor in Human Respiratory Epithelial Cells and a Potential Therapeutic Target in Small Cell Lung Cancer

“…The Lu-iPSC exhibited similarities to other pluripotent cell lines reported in the literature (13) including surface antigen and stem cell gene expression profiles, in-vitro growth, and teratoma formation. Although previously reported to be activated in stem cells (36, 37), cancer-germline genes commonly up-regulated in lung cancers remained transcriptionally repressed in Lu-iPSC. These unexpected findings are consistent with a report by Loriot et al .…”

KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes

“…For instance, MAGE-A and N-RAGE (also known as MAGE-D1) were expressed by mesenchymal stem cells, but their expression levels decreased upon the differentiation of stem cells [37]. Similarly, the expression of MAGE-A3 and -A6 were detected in embryonic stem cells, but not in differentiated derivatives [38]. In addition, global gene expression analysis of CD133 + cells isolated from four different cord blood units identified trophinin as one of 32 genes that encode membrane proteins selectively expressed on CD133 + hematopoietic stem cells [39].…”

Expression of cancer-testis antigens of Mage-a and Mage-b families in mouse embryonic fibroblasts cultured in vitro

“…Vavilova 26, Moscow, 119334 Russia e mail: olgagordeeva@yandex.ru Expression of CTAs of MAGE families was mainly studied in various tumor cells in vitro or in the clinical samples of tumors of different origin (Sahin et al, 2000;Yuasa et al, 2001). However, there is no evi dence about their expression in the normal cells during prolonged culturing in vitro (Cronwright et al, 2005;Gjerstorff et al, 2008;Lifantseva et al, 2011). In our previous study, we assumed that expression of CTAs of MAGE families can be associated with development of early embryonic lines; whereas their aberrant expression can be associated with pathological pro cesses, particularly transformation and carcinogenesis .…”

“…Thus, it was found that Mage a and GAGE genes are specifically expressed during the development of human male and female germ cells (De Plaen et al, 1999;Aubry et al, 2001;Gaskell et al, 2004;Gjerstorff et al, 2006Gjerstorff et al, , 2007. Expression of the MAGE/Mage genes was revealed in human and mice pluripotent stem cells, as well as in the develop ing human neuroectodermal and mesodermal cells, and the human placenta cells (Andrieu et al, 2003;Deponti et al, 2007;Jungbluth et al, 2007;Kuwajima et al, 2006;Gjerstorff et al, 2008;Lifantseva et al, 2011).…”