Generation of an enriched pool of DNA aptamers for an HER2‐overexpressing cell line selected by Cell SELEX

Dastjerdi, Kazem; Tabar, Gholamreza Hashemi; Dehghani, Hesam; Haghparast, Alireza

doi:10.1002/bab.36

Cited by 38 publications

(27 citation statements)

References 36 publications

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“…MCF-7 cells were cultured in DMEM supplemented with 10% FCS at 37°C in a 5% CO 2 incubator. The phenotypic features of those cell lines were well documented [12,13].…”

Section: Cell Linesmentioning

confidence: 93%

Mechanistic analysis of the antitumor efficacy of human natural killer cells against breast cancer cells

Kajitani

Tanaka

Arihiro

et al. 2012

Breast Cancer Res Treat

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We investigated the role of human natural killer (NK) cells in the peripheral blood (PB) and liver in controlling breast cancer. The proportion of NK cells among liver mononuclear cells was significantly higher than among PB mononuclear cells. Liver NK cells inductively expressed higher levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) than PB NK cells in response to interleukin-2 (IL-2). Liver NK cells displayed higher cytotoxicity against various breast cancer cell lines (MDA-MB231, MDA-MB453, MDA-MB468, and MCF-7) after IL-2 stimulation than did PB NK cells. Anti-HER2 monoclonal antibody (mAb) promoted the cytotoxicity of both the types of NK cells toward HER2-expressing cell lines. All breast cancer cell lines highly expressed death-inducing TRAIL receptors, death receptor 4, but did not express death-inhibitory receptors (DcR1 and DcR2). Both PB and liver NK cell-induced cytotoxicity was inhibited partially by anti-TRAIL mAb and more profoundly by the combination of anti-TRAIL mAb and concanamycin A, indicating that TRAIL and perforin are involved. IL-2-stimulated liver and PB NK cells exhibited upregulated expression of CXCR3, which bind to the chemokines CXCL9, CXCL10, and CXCL11 secreted by breast cancer cells. We also found that IFN-γ promoted the production of CXCL10 from breast cancer cells. The results of this study show that IFN-γ secreted from NK cells likely promotes the production of CXCL10 from breast cancer cells, which in turn accelerates the migration of CXCR3-expressing NK cells into the tumor site. These findings suggest the possibility of a therapeutic approach by either activation of endogenous PB and liver NK cells or adoptive transfer of in vitro-activated autologous NK cells.

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“…MCF-7 cells were cultured in DMEM supplemented with 10% FCS at 37°C in a 5% CO 2 incubator. The phenotypic features of those cell lines were well documented [12,13].…”

Section: Cell Linesmentioning

confidence: 93%

Mechanistic analysis of the antitumor efficacy of human natural killer cells against breast cancer cells

Kajitani

Tanaka

Arihiro

et al. 2012

Breast Cancer Res Treat

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“…So far, several anti-ErbB-specific aptamers have been developed (10)(11)(12)(13)(14). They generally show high affinity and specificity to their targets and, in the case of ErbB-1-and ErbB-3-specific aptamers, they also inhibit the proliferation of cultured cancer cells (10,14).…”

mentioning

confidence: 99%

Aptamer to ErbB-2/HER2 enhances degradation of the target and inhibits tumorigenic growth

Mahlknecht

Maron²,

Mancini

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

143

142

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Aptamers, oligonucleotides able to avidly bind cellular targets, are emerging as promising therapeutic agents, analogous to monoclonal antibodies. We selected from a DNA library an aptamer specifically recognizing human epidermal growth factor receptor 2 (ErbB-2/HER2), a receptor tyrosine kinase, which is overexpressed in a variety of human cancers, including breast and gastric tumors. Treatment of human gastric cancer cells with a trimeric version (42 nucleotides) of the selected aptamer (14 nucleotides) resulted in reduced cell growth in vitro, but a monomeric version was ineffective. Likewise, when treated with the trimeric aptamer, animals bearing tumor xenografts of human gastric origin reflected reduced rates of tumor growth. The antitumor effect of the aptamer was nearly twofold stronger than that of a monoclonal anti-ErbB-2/HER2 antibody. Consistent with aptamer-induced intracellular degradation of ErbB-2/HER2, incubation of gastric cancer cells with the trimeric aptamer promoted translocation of ErbB-2/HER2 from the cell surface to cytoplasmic puncta. This translocation was associated with a lysosomal hydrolase-dependent clearance of the ErbB-2/HER2 protein from cell extracts. We conclude that targeting ErbB-2/HER2 with DNA aptamers might retard the tumorigenic growth of gastric cancer by means of accelerating lysosomal degradation of the oncoprotein. This work exemplifies the potential pharmacological utility of aptamers directed at cell surface proteins, and it highlights an endocytosis-mediated mechanism of tumor inhibition.T he epidermal growth factor related protein (ErbB) family of receptor tyrosine kinases plays an important role in epitheliogenesis and, accordingly, serves as a major therapeutic target in several cancers. The family comprises four transmembrane receptors and 11 ligands that induce homodimerization or heterodimerization upon binding to the respective receptor (1). ErbB-1 (also called the epidermal growth factor receptor; EGFR) and ErbB-4 share some ligands, whereas no similar ligand is so far known for ErbB-2. Overexpression and mutations of ErbB family members lead to a multitude of malignancies. To date, synthetic tyrosine kinase inhibitors (e.g., Erlotinib and Gefitinib), as well as monoclonal antibodies (mAbs; e.g., Cetuximab and Trastuzumab), have been developed to inhibit pathological signaling or recruit the immune system to cancer cells (2). Aptamers might represent an alternative therapeutic modality. These molecules are small, singlestranded DNA or RNA molecules (3). RNA aptamers were described for the first time in 1990 by two laboratories (4, 5). Since then, aptamers against a multitude of different organic and inorganic, small and macromolecular, targets were developed. In addition, high-affinity aptamer binding ranging from picomolar to low nanomolar concentrations have been documented (6). Aptamers are selected in an evolutionary process called systematic evolution of ligands by exponential enrichment (SELEX). A DNA or RNA library containing single-stranded random ...

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“…Kim et al [36] developed an RNA aptamer using HER2 protein as the target and proposed that the selected aptamer could potentially be utilized in constructing novel imaging agents for HER2-positive tumors. Kazem et al [37] obtained a library of DNA aptamers using HER2-positive cells as the target for aptamer selection. Liu et al [18] developed a DNA aptamer that could selectively deliver doxorubicin to HER2-positive cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

Selection of a novel DNA thioaptamer against HER2 structure

Duan

Cao

et al. 2015

Clin Transl Oncol

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Generation of an enriched pool of DNA aptamers for an HER2‐overexpressing cell line selected by Cell SELEX

Cited by 38 publications

References 36 publications

Mechanistic analysis of the antitumor efficacy of human natural killer cells against breast cancer cells

Mechanistic analysis of the antitumor efficacy of human natural killer cells against breast cancer cells

Aptamer to ErbB-2/HER2 enhances degradation of the target and inhibits tumorigenic growth

Selection of a novel DNA thioaptamer against HER2 structure

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