MAGE‐C1/CT‐7 expression in plasma cell myeloma: Sub‐cellular localization impacts on clinical outcome

Tinguely, Marianne; Jenni, Bettina; Knights, Ashley; Lopes, BA; Korol, Dimitri; Rousson, Valentin; Curioni-Fontecedro, Alessandra; Cogliatti, Sergio; Bittermann, Anne Greet; Schmid, U; Dommann-Scherrer, Corina; Maurer, Robert; Renner, Christoph; Probst‐Hensch, Nicole; Moch, H.; Knuth, Alexander; Zippelius, Alfred

doi:10.1111/j.1349-7006.2008.00738.x

Cited by 40 publications

(49 citation statements)

References 25 publications

(34 reference statements)

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“…30 Also, GAGE1 and CTAG1B immunoreactivity is both nuclear and cytoplasmic, whereas MAGEC1 immunoreactivity is only cytoplasmic without nuclear expression. 20,48 In conclusion, we found an early loss of cancer testis antigen expression (MAGEA3, MAGEA4, MAGEC1, GAGE1 and CTAG1B) in intratubular germ cell neoplasia and a re-expression in a subset of classic seminomas in contrast to spermatocytic seminomas, which were strongly positive for the cancer testis antigens mentioned above. We provide evidence that there are different phenotypic patterns of tumorigenesis in classic and spermatocytic seminomas.…”

Section: Discussionmentioning

confidence: 52%

Cancer testis antigen expression in testicular germ cell tumorigenesis

et al. 2014

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Cancer testis antigens are encoded by germ line-associated genes that are present in normal germ cells of testis and ovary but not in differentiated tissues. Their expression in various human cancer types has been interpreted as 're-expression' or as intratumoral progenitor cell signature. Cancer testis antigen expression patterns have not yet been studied in germ cell tumorigenesis with specific emphasis on intratubular germ cell neoplasia unclassified as a precursor lesion for testicular germ cell tumors. Immunohistochemistry was used to study MAGEA3, MAGEA4, MAGEC1, GAGE1 and CTAG1B expression in 325 primary testicular germ cell tumors, including 94 mixed germ cell tumors. Seminomatous and non-seminomatous components were separately arranged and evaluated on tissue microarrays. Spermatogonia in the normal testis were positive, whereas intratubular germ cell neoplasia unclassified was negative for all five CT antigens. Cancer testis antigen expression was only found in 3% (CTAG1B), 10% (GAGE1, MAGEA4), 33% (MAGEA3) and 40% (MAGEC1) of classic seminoma but not in nonseminomatous testicular germ cell tumors. In contrast, all spermatocytic seminomas were positive for cancer testis antigens. These data are consistent with a different cell origin in spermatocytic seminoma compared with classic seminoma and support a progression model with loss of cancer testis antigens in early tumorigenesis of testicular germ cell tumors and later re-expression in a subset of seminomas.

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Section: Discussionmentioning

confidence: 52%

Cancer testis antigen expression in testicular germ cell tumorigenesis

et al. 2014

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“…12 Also GAGE1 and CTAG1B (NY-ESO-1) immunoreactivity is both nuclear and cytoplasmic, whereas MAGEC1 immunoreactivity is only cytoplasmic without nuclear expression. 6,23 In contrast, the MAGEC2 antibody showed an exclusive nuclear staining pattern. The staining was very intense, distinct and with little background so that cells expressing MAGEC2 was unmistakable.…”

Section: Discussionmentioning

confidence: 86%

MAGEC2 is a sensitive and novel marker for seminoma: a tissue microarray analysis of 325 testicular germ cell tumors

et al. 2011

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Melanoma-associated gene C2 (MAGEC2) is a recently identified cancer testis antigen expressed in normal testicular and placental tissue. It has been detected in some human carcinomas, but its expression in primary testicular germ cell tumors is unknown. Immunohistochemistry was used to study MAGEC2 protein in 325 primary testicular germ cell tumors, including 94 mixed germ cell tumors. Seminomatous and nonseminomatous components were separately arranged and evaluated on tissue microarrays. MAGEC2 expression was compared with POU5F1 (OCT3/4), SOX2, SOX17, KIT and TNFRSF8 (CD30). The mouse monoclonal anti-MAGEC2 antibody (clone LX-CT10.5) revealed a nuclear MAGEC2 expression with little or no background staining. MAGEC2 expression was found in 238 of 254 seminomas (94%), but not in embryonal carcinomas (n ¼ 89). POU5F1 (OCT3/4) was positive in 97% of seminomas and all embryonal carcinomas. In contrast, KIT was positive in 94% of seminoma but also in 8% of embryonal carcinomas. TNFRSF8 (CD30) and SOX2 were negative in seminoma and positive in embryonal carcinoma (96 and 90%, respectively). SOX17 was positive in 94% of seminoma and negative in embryonal carcinoma. We conclude that MAGEC2 allows a reliable distinction of seminoma from embryonal carcinomas. Therefore, MAGEC2 represents an additional tool for the differential diagnosis of testicular germ cell tumors.

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“…32,33 In addition, recent findings had suggested that an increased expression of MAGE-C1/CT7 or MAGE-A3 in MM patients was associated with a higher proportion of proliferating plasma cells in the bone marrow. 11,15 Finally, microarray analyses of MM samples had suggested an association between CT antigen expression and the expression of proliferation-associated genes.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 However, MM probably represents the malignancy with the richest CT antigen expression of all human cancers and the two CT antigens most frequently expressed in MM are MAGE-A3 and MAGE-C1/CT7. [10][11][12][13][14][15] MAGE-A3 is also expressed in a wide variety of solid tumors. It is a cytoplasmic protein with a molecular weight of 35 kDa 16 which was discovered analyzing CD8 + T-cell reactivity of a cancer patient against an autologous melanoma cell line.…”

Section: Introductionmentioning

confidence: 99%

Cancer-testis antigens MAGE-C1/CT7 and MAGE-A3 promote the survival of multiple myeloma cells

Atanackovic¹,

Hildebrandt²,

Jadczak³

et al. 2009

Haematologica

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BackgroundMultiple myeloma is a life-threatening disease and despite the introduction of stem cell transplantation and novel agents such as thalidomide, lenalidomide, and bortezomib most patients will relapse and develop chemoresistant disease. Therefore, alternative therapeutic modes for myeloma are needed and cancer-testis antigens such as MAGE-C1/CT7 and MAGE-A3 have been suggested to represent a class of tumor-specific proteins particularly suited for targeted immunotherapies. Surprisingly, the biological role of cancer-testis genes in myeloma remains poorly understood. Design and MethodsWe performed the first investigation of the function of two cancer-testis antigens most commonly expressed in myeloma, MAGE-C1/CT7 and MAGE-A3, using an RNA interferencebased gene silencing model in myeloma cell lines. Functional assays were used to determine changes in proliferation, cell adhesion, chemosensitivity, colony formation, and apoptosis resulting from gene-specific silencing. ResultsWe show that the investigated genes are not involved in regulating cell proliferation or adhesion; however, they play an important role in promoting the survival of myeloma cells. Accordingly, knock-down of MAGE-C1/CT7 and MAGE-A3 led to the induction of apoptosis in the malignant plasma cells and, importantly, both genes were also essential for the survival of clonogenic myeloma precursors. Finally, silencing of cancer-testis genes further improved the response of myeloma cells to conventional therapies. ConclusionsCancer-testis antigens such as MAGE-C1/CT7 and MAGE-A3 play an important role in promoting the survival of myeloma cells and clonogenic precursors by reducing the rate of spontaneous and chemotherapy-induced apoptosis and might, therefore, represent attractive targets for novel myeloma-specific therapies.Key words: cancer-testis antigens, gene function, RNAi, apoptosis, tumor immunology, multiple myeloma, stem cell transplantation.Citation: Atanackovic D, Hildebrandt Y, Jadczak A, Cao Y, Luetkens T, Meyer S, Kobold S, Bartels K, Pabst C, Lajmi N, Gordic M, Stahl T, Zander AR, Bokemeyer C, promote the survival of multiple myeloma cells. Haematologica 2010;95:785-793. doi:10.3324/haematol.2009 This is an open-access paper. © F e r r a t a S t o r t i F o u n d a t i o n Cancer-testis antigens MAGE-C1/CT7 and MAGE-A3 promote the survival of multiple myeloma cells

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MAGE‐C1/CT‐7 expression in plasma cell myeloma: Sub‐cellular localization impacts on clinical outcome

Cited by 40 publications

References 25 publications

Cancer testis antigen expression in testicular germ cell tumorigenesis

Cancer testis antigen expression in testicular germ cell tumorigenesis

MAGEC2 is a sensitive and novel marker for seminoma: a tissue microarray analysis of 325 testicular germ cell tumors

Cancer-testis antigens MAGE-C1/CT7 and MAGE-A3 promote the survival of multiple myeloma cells

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