CD109 is identified as a potential nasopharyngeal carcinoma biomarker using aptamer selected by cell-SELEX

Jia, Wei; Ren, Chao; Wang, Lei; Zhu, Bin; Jia, Wei Hua; Gao, Menghui; Zeng, Fei; Zeng, Liang; Xia, Xiaomeng; Zhang, Xiaobing; Fu, Ting; Li, Shasha; Du, Can; Jiang, Xingjun; Chen, Yuxiang; Tan, Weihong; Zhao, Zilong; Liu, Weidong

doi:10.18632/oncotarget.10530

Cited by 53 publications

(35 citation statements)

References 46 publications

(41 reference statements)

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“…High levels of CD109 expression have been detected in various tumor‐cell lines and tumor tissues, including those associated with squamous cell carcinomas (SCCs) of the lung, esophagus, uterus, and oral cavity, adenocarcinomas of the lung and pancreas, breast cancer, glioblastoma, hepatocellular carcinoma, urothelial carcinoma of the urinary bladder, and several types of sarcomas (Table ) . Immunohistochemical (IHC) analyses revealed elevated CD109 expression on tumor cells (Fig.…”

Section: Cd109 Is a Membrane Protein Expressed In Malignant Tumorsmentioning

confidence: 99%

CD109: a multifunctional GPI‐anchored protein with key roles in tumor progression and physiological homeostasis

Mii

Enomoto

Shiraki

et al. 2019

Pathology International

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CD109 is a glycosylphosphatidylinositol‐anchored glycoprotein and a member of the α2‐macroglobulin/C3,C4,C5 family of thioester‐containing proteins first identified as being expressed on blood cells, including activated T cells and platelets, and a subset of CD34 + bone marrow cells containing megakaryocyte progenitors. Although CD109 carries the biallelic platelet‐specific alloantigen Gov, the physiological functions or roles of CD109 in human disease remain largely unknown. It was recently demonstrated that CD109 is expressed in many malignant tumors, including various squamous cell carcinomas and adenocarcinomas, and plays a role as a multifunctional coreceptor. CD109 reportedly associates with transforming growth factor (TGF)‐β receptors and negatively regulates TGF‐β signaling in keratinocytes. Additionally, CD109 is potentially related to signal transducer and activator of transcription‐3 signaling and aberrant cell proliferation. In this review, we describe recent evidence of CD109‐specific significance in malignant tumors shown in mouse models and human tissues. Furthermore, we discuss the physiological functions of CD109 in vitro and in vivo, including results of phenotype analyses of CD109‐deficient mice exhibiting epidermal hyperplasia and osteopenia.

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Section: Cd109 Is a Membrane Protein Expressed In Malignant Tumorsmentioning

confidence: 99%

CD109: a multifunctional GPI‐anchored protein with key roles in tumor progression and physiological homeostasis

Mii

Enomoto

Shiraki

et al. 2019

Pathology International

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“…To discover potential biomarkers for NPC, untargeted naïve cell-SELEX is employed, and the aptamer-binding ligands is retrieved by pull-down assay and identified by LC-MS/MS. The NPC aptamers bind the cell surface biomarker CD109 (43). The CD109 aptamers show specificity for CD109 on the cell surface of NPC cell lines and clinical NPC tissue specimens, but not for normal nasopharyngeal cell line and clinic normal nasopharyngeal tissues that expressed little to no CD109.…”

Section: Novel Biomarker Discoverymentioning

confidence: 99%

Emerging cancer-specific therapeutic aptamers

Yoon¹,

Rossi

2017

Current Opinion in Oncology

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Purpose of review We will describe recently discovered smart aptamers with tumor specificity, with an emphasis on targeted delivery of novel therapeutic molecules, cancer-specific biomarkers, and immunotherapy. Recent findings The development of cancer-specific aptamers has facilitated targeted delivery of potent therapeutic molecules to cancer cells without harming non-tumoral cells. This specificity also makes it possible to discover novel cancer biomarkers. Furthermore, alternative immune-checkpoint blockade aptamers have been developed for combinational immunotherapy. Summary Aptamers selected against cancer cells show cancer specificity, which has great potential for targeting. First, functionalizing targeted aptamers with therapeutic molecule payloads (e.g., small activating RNAs (saRNAs), anti-mitotic drugs, therapeutic antibodies, and peptides) facilitates successful delivery into cancer cells. This approach greatly improves the therapeutic index by minimizing side effects in non-tumoral cells. Second, cancer-specific proteins have been identified as cancer biomarkers through in vitro and in vivo selection, aptamer pull-down assays, and mass spectrometry. These newly discovered biomarkers improve therapeutic intervention and diagnostic specificity. In addition, the development of alternative immune-checkpoint blockade aptamers are suggested for use in combinational immunotherapeutic with current immune blockade regimens, to reduce the resistance and exhaustion of T cells in clinical trials.

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“…There were a lot of researches using Cell‐SELEX against membrane proteins has already been used in a significant number of studies, and the developed aptamers have proven useful for identification of various target proteins, such as TGF‐Beta‐1‐Binding Protein CD109 (Jia et al, ), B‐lymphocyte antigen CD20 (Al‐Youssef, Ghobadloo, & Berezovski, ), RET receptor tyrosine kinase (Cerchia et al, ), haemagglutinin on the surface of human influenza viruses (Gopinath et al, ), growth factor‐β type III receptor (Ohuchi et al, ), and protein tyrosine phosphatase 1B (Townshend, Aubry, Marcellus, Gehring, & Tremblay, ). In addition, aptamers against cell surface proteins are useful as biomarkers.…”

Section: Aptamer Generation Against Cells and Tissuesmentioning

confidence: 99%

“…There were a lot of researches using Cell-SELEX against membrane proteins has already been used in a significant number of studies, and the developed aptamers have proven useful for identification of various target proteins, such as TGF-Beta-1-Binding Protein CD109 (Jia et al, 2016), B-lymphocyte antigen CD20 (Al-Youssef, Ghobadloo, & Berezovski, 2016), RET receptor tyrosine kinase (Cerchia et al, 2005), haemagglutinin on the surface of human influenza viruses (Gopinath et al, 2006), growth factor-β type III receptor (Ohuchi et al, 2006), and protein tyrosine phosphatase 1B (Townshend, Aubry, Marcellus, Gehring, & Tremblay, 2010). In Aptamers generated against target transmembrane proteins expressed in prokaryotic cells do not interact with the same proteins expressed in eukaryotic cells, as the latter undergo different posttranslational modifications that render their epitopes inaccessible to aptamers generated against proteins expressed in prokaryotic cells.…”

Section: Cell-selexmentioning

confidence: 99%

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Development of aptamers against unpurified proteins

Goto

Tsukakoshi

2017

Biotech & Bioengineering

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SELEX (Systematic Evolution of Ligands by EXponential enrichment) has been widely used for the generation of aptamers against target proteins. However, its requirement for pure target proteins remains a major problem in aptamer selection, as procedures for protein purification from crude bio-samples are not only complicated but also time and labor consuming. This is because native proteins can be found in a large number of diverse forms because of posttranslational modifications and their complicated molecular conformations. Moreover, several proteins are difficult to purify owing to their chemical fragility and/or rarity in native samples. An alternative route is the use of recombinant proteins for aptamer selection, because they are homogenous and easily purified. However, aptamers generated against recombinant proteins produced in prokaryotic cells may not interact with the same proteins expressed in eukaryotic cells because of posttranslational modifications. Moreover, to date recombinant proteins have been constructed for only a fraction of proteins expressed in the human body. Therefore, the demand for advanced SELEX methods not relying on complicated purification processes from native samples or recombinant proteins is growing. This review article describes several such techniques that allow researchers to directly develop an aptamer from various unpurified samples, such as whole cells, tissues, serum, and cell lysates. The key advantages of advanced SELEX are that it does not require a purification process from a crude bio-sample, maintains the functional states of target proteins, and facilitates the development of aptamers against unidentified and uncharacterized proteins in unpurified biological samples.

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CD109 is identified as a potential nasopharyngeal carcinoma biomarker using aptamer selected by cell-SELEX

Cited by 53 publications

References 46 publications

CD109: a multifunctional GPI‐anchored protein with key roles in tumor progression and physiological homeostasis

CD109: a multifunctional GPI‐anchored protein with key roles in tumor progression and physiological homeostasis

Emerging cancer-specific therapeutic aptamers

Development of aptamers against unpurified proteins

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