Enhanced expression of cancer testis antigen genes in glioma stem cells

Yawata, Toshio; Nakai, Eiichi; Park, Kae Chang; Chihara, Takahiro; Kumazawa, Ayano; Toyonaga, Shinichi; Masahira, Takanori; Nakabayashi, Hiromichi; Kaji, Takao; Shimizu, Katsuji

doi:10.1002/mc.20614

Cited by 32 publications

(30 citation statements)

References 35 publications

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“…Finally, CTA expression has been reported in cancer stem cells, among others in melanoma and glioma. 47,48 In MM, a putative cancer stem cell has been reported, and may be CD19+CD138-ve. 49,51 The putative importance of CTA genes in these cells is subject to future investigation.…”

Section: Discussionmentioning

confidence: 99%

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Duin¹,

Broyl²,

Knegt³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundIn multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens which can be classified by varying expression in normal tissue: restricted to testis, expressed in testis and brain and not restricted but selectively expressed in testis. Design and MethodsEvaluation of cancer testis antigen expression was made in newly diagnosed multiple myeloma cases (HOVON-65/GMMG-HD4 trial; n=320) and in relapse cases (APEX, SUMMIT, CREST trials; n=264). Presence of expression using Affymetrix GeneChips was determined for 123 cancer testis antigens. Of these 87 had a frequency of more than 5% in the newly diagnosed and relapsed patients, and were evaluated in detail. ResultsTissue restriction was known for 58 out of 87 cancer testis antigens. A significantly lower frequency of presence calls in the relapsed compared to newly diagnosed cases was found for 3 out of 13 testis restricted genes, 2 out of 7 testis/brain restricted genes, and 17 out of 38 testis selective genes. MAGEC1, MAGEB2 and SSX1 were the most frequent testis-restricted cancer testis antigens in both data sets. Multivariate analysis demonstrated that presence of MAGEA6 and CDCA1 were clearly associated with shorter progression free survival, and presence of MAGEA9 with shorter overall survival in the set of newly diagnosed cases. In the set of relapse cases, presence of CTAG2 was associated with shorter progression free survival and presence of SSX1 with shorter overall survival. ConclusionsRelapsed multiple myeloma reveals extensive cancer testis antigen expression. Cancer testis antigens are confirmed as useful prognostic markers in newly diagnosed multiple myeloma patients and in relapsed multiple myeloma patients.The HOVON-65/GMMG-HD4 trial is registered under Dutch trial register n. respectively.

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Section: Discussionmentioning

confidence: 99%

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Duin¹,

Broyl²,

Knegt³

et al. 2011

Haematologica

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“…CD133 expression has been suggested as a marker of stemness in this malignancy based on the observation that CD133 positive cells can give rise to tumorigenic cells [58,59].…”

Section: Cancer Testis Antigensmentioning

confidence: 99%

“…Interestingly, CTAs such as LAGE-1, NY-ESO-1 and MAGE family members are also expressed in GBM CD133 positive cells, compared with differentiated or parent cells [59].…”

Section: Cancer Testis Antigensmentioning

confidence: 99%

“…Moreover, the expression of MAGE family members and CD133 is down-regulated as cells become more differentiated, indicating a correlation between expression of these molecules and the undifferentiated cellular state [59]. Since CD133 negative GBM cells can also be tumorigenic [58], CD133 expression can't be considered a specific marker for GBM stemness.…”

Section: Cancer Testis Antigensmentioning

confidence: 99%

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Targeting Tumor Initiating Cells through Inhibition of Cancer Testis Antigens and Notch Signaling: A Hypothesis

Colombo

Mirandola²,

Reidy

et al. 2015

International Reviews of Immunology

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Tumor initiating cells (TICs) differ from normal stem cells (SCs) in their ability to initiate tumorigenesis, invasive growth, metastasis and the acquisition of chemo and/or radio-resistance. In the last years, several studies have indicated the potential role of the Notch system as a key regulator of cellular stemness and tumor development.Furthermore, the expression of cancer testis antigens (CTA) in TICs, and their role in SC differentiation and biology, has become an important area of investigation. Here we propose a model in which CTA expression and Notch signaling interacts to maintain the sustainability of self-replicating tumor populations, ultimately leading to the development of metastasis, drug resistance, and cancer progression. We hypothesize that Notch-CTA interactions in TICs offer a novel opportunity for meaningful therapeutic interventions in cancer.

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“…This may point to the widespread expression of BORIS which is not restricted to cancerous cell lines. In addition, it has been found that the expression of some CT genes does not rely on the presence of BORIS [12,17,48,49], and thus, it is unlikely that BORIS would be a major CT gene inducing factor [50]. Furthermore, some more general biological functions including a regulatory role in normal cell division have been proposed for BORIS [47], which leads to a significant decrease in cell proliferation and clonogenic capacity.…”

Section: Introductionmentioning

confidence: 99%

Expression analysis of BORIS during pluripotent, differentiated, cancerous, and non-cancerous cell states

Soltanian

Dehghani

Matin

et al. 2014

ABBS

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BORIS/CTCFL is an 11 zinc finger protein, which is the paralog of CTCF, a ubiquitously expressed protein with diverse roles in gene expression and chromatin organization. Several studies have shown that the expression of BORIS is restricted to normal adult testis, pluripotent cells, and diverse cancer cell lines. Thus, it is known as a cancer-testis (CT) gene that has been hypothesized to exhibit oncogenic properties and to be involved in cancer cell proliferation. On the contrary, other reports have shown that its expression is more widespread and can be detected in differentiated and normal somatic cells; hence, it might have roles in general cellular functions. The present study was aimed to analyze the expression of BORIS in different cell states of pluripotent, differentiated, cancerous and non-cancerous. We found that the two cell states of pluripotency and differentiation are not accompanied with significant variations of BORIS expression. Furthermore, Boris transcripts were detected at approximately the same level in cancer and non-cancer cell lines. These findings suggest that, in contrast to some previous reports, the expression of mouse BORIS is not limited to only cancerous cells or pluripotent cell states.

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Enhanced expression of cancer testis antigen genes in glioma stem cells

Cited by 32 publications

References 35 publications

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Targeting Tumor Initiating Cells through Inhibition of Cancer Testis Antigens and Notch Signaling: A Hypothesis

Expression analysis of BORIS during pluripotent, differentiated, cancerous, and non-cancerous cell states

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