D2-40 antibody immunoreactivity in developing human brain, brain tumors and cultured neural cells

Department of Pathology, St Mary's Hospital, Tsubukuhon-machi, Kurume-shi, and Department of Pathology and Biodefense, Saga Medical School, Japan.
Modern Pathology (Impact Factor: 6.19). 08/2006; 19(7):974-85. DOI: 10.1038/modpathol.3800616
Source: PubMed


D2-40 antibody is raised against an oncofetal antigen, the M2A antigen. It has been used as a marker for lymphatic endothelium as well as mesothelioma and cerebellar hemangioblastoma. We demonstrate here that positive D2-40 immunoreactivity was found in the developing cerebrum, particularly in the germinal matrix layer, immature ependyma, choroid plexus and meninges. In the developing cerebellum, positive D2-40 immunoreactivity was found in the external granular layer particularly of the outer portion and the Purkinje cell layer as well as meninges. Some brain tumors such as anaplastic ependymoma, some medulloblastomas, glioblastoma, pineal germinoma, craniopharyngioma, choroid plexus papilloma, choroid plexus carcinoma, and meningioma showed positive immunoreactivity with D2-40. Therefore, D2-40 antibody is considered a useful marker for research on developing brain and diagnosis of brain tumors, differentiation between choroid plexus carcinoma and metastatic carcinoma. In addition, on cultured human neural cells, D2-40 immunoreactivity was found in nestin-positive neural stem/progenitor cells and neuronal lineage cells. As D2-40 antibody recognizes cell surface antigen M2A, it might be a candidate cell surface marker for isolation of human neural stem cells/neuronal lineage cells in the fluorescence-activated cell sorting technique.

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Available from: Mami Yamasaki, Apr 10, 2014
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    • "D2-40 has been found to stain a diverse collection of normal and neoplastic tissues. In recent years, it has been utilized widely as an immunohistochemical marker for lymphatic endothelium as well as mesothelioma and germ cell tumors [13, 17, 23, 24]. "
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    ABSTRACT: Background. Meningiomas are common intracranial tumors. Recently, histogenetic and phenotypic similarities between meningiomas and mesotheliomas have been proposed. We were interested in whether these similarities are reflected on the immunohistochemical level, which would add new potentially diagnostic markers for meningiomas. Methods. The expression of mesothelioma-related markers (D2-40, Calretinin, Keratin 5/6, WT1, and Methotheioma-Ab1) was investigated in 87 cases of meningiomas and compared to EMA expression. Results. 73.6% of meningioma cases were grade I, 20.7% were grade II, and 5.7% were grade III. 83.9% of meningioma cases were classical and 16.1% had special nonmeningothelial features. D2-40 was expressed in 37.9% of cases and was significantly restricted to classical meningiomas. Calretinin and WT1 were negative while Keratin 5/6 and Mesothelioma-Ab1 were weakly expressed in classical variants (5.7% and 3.4%, resp.). EMA was consistently expressed in all cases. Its expression was significantly higher than that of mesothelioma-related markers; this held true also when D2-40 expression was considered separately. Conclusions. Mesothelioma-related markers are not extensively expressed in meningiomas, a finding that argues against their proposed histogenetic and phenotypic similarities. Compared to EMA, the significantly lower expression of mesothelioma-related markers and their restricted expression to classical meningioma variants hamper their potential future use as diagnostic markers for meningioma.
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    • "We and others previously reported that PDPN, which encodes the mucin-type transmembrane sialoglycoprotein podoplanin , is upregulated in glioblastoma and is correlated with invasion and malignancy in astrocytic tumors (Scrideli et al., 2008). Additionally, podoplanin was suggested as a putative marker for neural stem cells and progenitor cells (Nakamura et al., 2006). Podoplanin is overexpressed in a variety of cancers, including squamous cell carcinomas (Kato et al., 2005), malignant mesotheliomas (Ordonez, 2006), colorectal adenocarcinomas (Kato et al., 2003), and central nervous system tumors (Mishima et al., 2006; Shibahara et al., 2006). "
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    ABSTRACT: Glioblastoma is the most frequent and malignant brain tumor, characterized by an elevated capacity for cellular proliferation and invasion. Recently, it was demonstrated that podoplanin membrane sialo-glycoprotein encoded by PDPN gene is over-expressed and related to cellular invasion in astrocytic tumors; however the mechanisms of regulation are still unknown. MicroRNAs are noncoding RNAs that regulate gene expression and several biological processes and diseases, including cancer. Nevertheless, their roles in invasion, proliferation, and apoptosis of glioblastoma are not completely understood. In this study, we focused on miR-29b and miR-125a, which were predicted to regulate PDPN, and demonstrated that these microRNAs directly target the 3' untranslated region of PDPN and inhibit invasion, apoptosis, and proliferation of glioblastomas. Furthermore, we report that miR-29b and miR-125a are downregulated in glioblastomas and also in CD133-positive cells. Taken together, these results suggest that miR-29b and miR-125a represent potential therapeutic targets in glioblastoma.
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