Aggrus: a diagnostic marker that distinguishes seminoma from embryonal carcinoma in testicular germ cell tumors

Kato, Yukinari; Sasagawa, Isoji; Kaneko, Mika K.; Osawa, Motoki; Fujita, Naoya; Tsuruo, Takashi

doi:10.1038/sj.onc.1207869

Cited by 141 publications

(97 citation statements)

References 14 publications

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“…Genes/antigens preferentially expressed in SEM include PLAP (Hofmann et al, 1989), M2A (Marks et al, 1995), KIT (Strohmeyer et al, 1991;Rajpert-De Meyts and Skakkebaek, 1994; this study), cyclin D2 (CCND2) (Houldsworth et al, 1997;Bartkova et al, 1999;Okada et al, 2003), MAGE-A4 (Aubry et al, 2001), HIWI (Qiao et al, 2002), DAZL-1 (LifschitzMercer et al, 2002), TFCP2L1 (this study), Aggrus (Kato et al, 2004) and JUP . The emerging expression pattern of N-SEMs is more complex, and because of histological variability of these tumours, a distinct 'signature' may not exist for this entity.…”

Section: Discussionmentioning

confidence: 76%

“…This is consistent with recent reports on widespread expression of transcripts from both strands in large parts of the human genome (Kapranov et al, 2002;Cawley et al, 2004), and we speculate that this feature may contribute to the heterogeneity of overt tumours -especially N-SEMs. Even protein expression has earlier been reported to be markedly heterogeneous in TGCTs, including CIS (Rajpert-De Meyts et al, 1996;LifschitzMercer et al, 2002;Hoei-Hansen et al, 2004b;Kato et al, 2004). It is, however, evident from the RT -PCR results shown in Figure 2 that by combining results from a range of different genes, a TGCT sample could be classified as a SEM or N-SEM.…”

Section: Discussionmentioning

confidence: 90%

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Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

et al. 2005

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The carcinoma in situ (CIS) cell is the common precursor of nearly all testicular germ cell tumours (TGCT). In a previous study, we examined the gene expression profile of CIS cells and found many features common to embryonic stem cells indicating that initiation of neoplastic transformation into CIS occurs early during foetal life. Progression into an overt tumour, however, typically first happens after puberty, where CIS cells transform into either a seminoma (SEM) or a nonseminoma (N-SEM). Here, we have compared the genome-wide gene expression of CIS cells to that of testicular SEM and a sample containing a mixture of N-SEM components, and analyse the data together with the previously published data on CIS. Genes showing expression in the SEM or N-SEM were selected, in order to identify gene expression markers associated with the progression of CIS cells. The identified markers were verified by reverse transcriptase -polymerase chain reaction and in situ hybridisation in a range of different TGCT samples. Verification showed some interpatient variation, but combined analysis of a range of the identified markers may discriminate TGCT samples as SEMs or NSEMs. Of particular interest, we found that both DNMT3B (DNA (cytosine-5-)-methyltransferase 3 beta) and DNMT3L (DNA (cytosine-5-)-methyltransferase 3 like) were overexpressed in the N-SEMs, indicating the epigenetic differences between N-SEMs and classical SEM.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 90%

Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

et al. 2005

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“…Monoclonal antibodies (Abs) for murine E-cadherin (ECCD2), murine VEGFR-2 (AVAS12), and murine podoplanin were prepared as described previously 17,20 and labeled in our laboratory according to manufacturer instruction. Biotynated monoclonal Abs (MoAbs) for murine CD31 (Mec13.3) and MoAbs for VE-cad were purchased from BD Pharmingen.…”

Section: Reagents and Antibodiesmentioning

confidence: 99%

Differentiation of Lymphatic Endothelial Cells From Embryonic Stem Cells on OP9 Stromal Cells

Kono

Kubo

Shimazu

et al. 2006

ATVB

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Objectives— The discovery of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 (VEGFR-3) has started to provide an understanding of the molecular mechanisms of lymphangiogenesis. The homeobox gene prox1 has been proven to specify lymphatic endothelial cells (ECs) from blood ECs. We investigated the process of lymphatic EC (LEC) differentiation using embryonic stem (ES) cells. Methods and Results— VEGFR-2 + cells derived from ES cells differentiated into LECs at day 3 on OP9 stromal cells defined by the expression of prox1, VEGFR-3, and another lymphatic marker podoplanin. VEGFR-2 + cells gave rise to LYVE-1 + embryonic ECs, which were negative for prox1 on day 1 but turned to prox1 + LECs by day 3. VEGFR-3-Fc or Tie2-Fc, sequestering VEGF-C or angiopoietin1 (Ang1), suppressed colony formation of LECs on OP9 cells. However, addition of VEGF-C and Ang1 in combination with VEGF to the culture of VEGFR-2 + cells on collagen-coated dishes failed to induce LECs. LEC-inducing activity of OP9 cells was fully reproduced on paraformaldehyde-fixed OP9 cells with the conditioned medium. Conclusion— We succeeded in differentiating LECs from ES cells and revealed the requirements of VEGF-C, Ang1, and other unknown factors for LEC differentiation.

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“…It is overexpressed in several solid tumors, such as squamous cell carcinoma (21), malignant mesothelioma (22), Kaposi sarcoma, angiosarcoma (23), testicular seminoma (24), and brain tumors (25). PDPN expression is associated with malignant progression (25)(26)(27), epithelial-mesenchymal transition (27), and metastasis (26).…”

Section: Introductionmentioning

confidence: 99%

CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains

Shiina

Ohno

Ohka

et al. 2016

Cancer Immunology Research

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Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults with a 5-year overall survival rate of less than 10%. Podoplanin (PDPN) is a type I transmembrane mucin-like glycoprotein, expressed in the lymphatic endothelium. Several solid tumors overexpress PDPN, including the mesenchymal type of GBM, which has been reported to present the worst prognosis among GBM subtypes. Chimeric antigen receptor (CAR)-transduced T cells can recognize predefined tumor surface antigens independent of MHC restriction, which is often downregulated in gliomas. We constructed a lentiviral vector expressing a third-generation CAR comprising a PDPN-specific antibody (NZ-1-based single-chain variable fragment) with CD28, 4-1BB, and CD3z intracellular domains. CAR-transduced peripheral blood monocytes were immunologically evaluated by calcein-mediated cytotoxic assay, ELISA, tumor size, and overall survival. The generated CAR T cells were specific and effective against PDPN-positive GBM cells in vitro. Systemic injection of the CAR T cells into an immunodeficient mouse model inhibited the growth of intracranial glioma xenografts in vivo. CAR T-cell therapy that targets PDPN would be a promising adoptive immunotherapy to treat mesenchymal GBM.

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Aggrus: a diagnostic marker that distinguishes seminoma from embryonal carcinoma in testicular germ cell tumors

Cited by 141 publications

References 14 publications

Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

Differentiation of Lymphatic Endothelial Cells From Embryonic Stem Cells on OP9 Stromal Cells

CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains

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