Anti-CD44 DNA Aptamers Selectively Target Cancer Cells

Pęcak, Aleksandra; Skalniak, Łukasz; Pels, Katarzyna; Książek, Mirosław; Madej, Mariusz; Krzemień, Dobrosława; Malicki, Stanisłąw; Władyka, Benedykt; Dubin, Adam; Holak, Tad A.; Dubin, Grzegorz

doi:10.1089/nat.2019.0833

Cited by 14 publications

(6 citation statements)

References 55 publications

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“…Depending on the CD44–HA interaction, liver cancer cells were found to roll on HA enriched endothelial cells, an essential step during metastasis [ 139 ]. In acute myeloid leukaemia cells, the binding of CD44 and HA enhanced cell proliferation, and blocking this binding significantly inhibited the growth of CD44 + leukaemia cells [ 140 ]. The HA–CD44 axis also activated ERM, ankyrin, Grb2, Gab-1 and Vav2, which drive cell migration via RAS, RhoA and Rac GTPase families [ 120 , 133 , 136 , 141 ].…”

Section: Cd44 Receptor-ligand Interactionsmentioning

confidence: 99%

CD44: A Multifunctional Mediator of Cancer Progression

et al. 2021

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CD44, a non-kinase cell surface transmembrane glycoprotein, has been widely implicated as a cancer stem cell (CSC) marker in several cancers. Cells overexpressing CD44 possess several CSC traits, such as self-renewal and epithelial-mesenchymal transition (EMT) capability, as well as a resistance to chemo- and radiotherapy. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The interaction of such isoforms with ligands, particularly hyaluronic acid (HA), osteopontin (OPN) and matrix metalloproteinases (MMPs), drive numerous cancer-associated signalling. However, there are contradictory results regarding whether high or low CD44 expression is associated with worsening clinicopathological features, such as a higher tumour histological grade, advanced tumour stage and poorer survival rates. Nonetheless, high CD44 expression significantly contributes to enhanced tumourigenic mechanisms, such as cell proliferation, metastasis, invasion, migration and stemness; hence, CD44 is an important clinical target. This review summarises current research regarding the different CD44 isoform structures and their roles and functions in supporting tumourigenesis and discusses CD44 expression regulation, CD44-signalling pathways and interactions involved in cancer development. The clinical significance and prognostic value of CD44 and the potential of CD44 as a therapeutic target in cancer are also addressed.

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Section: Cd44 Receptor-ligand Interactionsmentioning

confidence: 99%

CD44: A Multifunctional Mediator of Cancer Progression

et al. 2021

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“…Such results indicate that 2c2s recognizes a different epitope at PD-L1 compared to the antibody and that the 2c2s recognized epitope is partially masked at a subpopulation of cells. Unlike the antibody, 2c2s was unable to dissociate the PD-1/PD-L1 at the cell surface (Figure S3) as tested using reporter assay described previously [11][12][13], again demonstrating that the antibody and 2c2s recognize different epitopes at PD-L1.…”

Section: Detection Of Pd-l1 At the Cell Surfacementioning

confidence: 57%

Imaging of Clear Cell Renal Carcinoma with Immune Checkpoint Targeting Aptamer-Based Probe

et al. 2022

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Immune checkpoint targeting immunotherapy has revolutionized the treatment of certain cancers in the recent years. Determination of the status of immune checkpoint expression in particular cancers may assist decision making. Here, we describe the development of a single-stranded aptamer-based molecular probe specifically recognizing human PD-L1. Target engaging aptamers are selected by iterative enrichment from a random ssDNA pool and the binding is characterized biochemically. Specificity and dose dependence is demonstrated in vitro in the cell culture using human kidney tumor cells (786-0), human melanoma cells (WM115 and WM266.4) and human glioblastoma LN18 cancer cells. The utility of the probe in vivo is demonstrated using two mouse tumor models, where we show that the probe exhibits excellent potential in imaging. We postulate that further development of the probe may allow universal imaging of different types of tumors depending on their PD-L1 status, which may find utility in cancer diagnosis.

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“…In another study, gefitinib-loaded nanomicelles with conjugation of this CD44 RNA aptamer inhibited spheroid formation of CD133-positive lung cancer cells [27]. The third published CD44 aptamer targeted also the HABD recombinant protein [28]. This CD44 DNA aptamer, named s5rev, exhibited a KD of 238 nM with cytotoxic effect shown on a leukemic cell line NB4, possibly via inhibiting the Akt pathway [28].…”

Section: Discussionmentioning

confidence: 97%

“…The third published CD44 aptamer targeted also the HABD recombinant protein [28]. This CD44 DNA aptamer, named s5rev, exhibited a KD of 238 nM with cytotoxic effect shown on a leukemic cell line NB4, possibly via inhibiting the Akt pathway [28].…”

Section: Discussionmentioning

confidence: 99%

Development of CD44E/s dual-targeting DNA aptamer as nanoprobe to deliver treatment in hepatocellular carcinoma

Lo¹,

Chan²,

Yu³

et al. 2022

Nanotheranostics

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Background: Hepatocellular carcinoma (HCC) is the predominant subtype of liver cancer with an extraordinary high mortality. Resistance to systemic therapy is a major cause of inferior clinical outcome in most patients with HCC. CD44 is a transmembrane cell-surface glycoprotein that is characterized by its variants displaying differential overexpression in human cancers. Aptamers, also known as chemical antibodies, can target cell-surface molecules with high affinity and specificity via structural recognition. Aptamer-mediated drug delivery hence is of high potentials in guiding therapy to improve efficacy. Methods: Variants CD44E and CD44s were studied for HCC relevance by investigating their expressions in primary HCC tumors, adjacent cirrhotic/fibrotic livers and normal livers using junction specific primers in qPCR assay. CD44E/s dual-targeted aptamers were uncovered by integrating loss-gain cell-SELEX and next generation sequencing. Selected aptamers were characterized for binding affinity and specificity, biostability, in vivo and in vitro cytotoxicity, in vivo homing and biodistribution, and ability to deliver 5-FU into targeted cells in vitro. Results: Both CD44E and CD44s isoforms showed significant upregulations in HCC tumors with CD44E/s activities promoting cell proliferation and migration. Loss-gain cell-SELEX uncover a CD44E/s dual-targeting aptamer, termed CD44-Apt1. Strong binding of CD44-Apt1 to cell-surface CD44 positive cells but not CD44-negative cells was demonstrated by flow-cytometry. CD44-Apt1 displayed strong affinity to CD44E and CD44s with KD as low as 1 nM but not the hyaluronic acid binding domain of CD44. Confocal imaging of CD44-positive cells stained with fluorescent-labeled CD44-Apt1 showed profound cytoplasmic localization, suggesting efficient cell-penetrating ability. Meanwhile, no apparent staining was observed in CD44-negative cells. CD44-Apt1 when conjugated with inhibitor 5-FU showed efficient guidance of 5-FU into HCC cells that significantly enhanced drug toxicity by more than thousands-fold. Both in vitro cell treatment and in vivo animal biodistribution indicated that CD44-Apt1 is non-toxic. In HCC xenograft model, CD44-Apt1 efficiently homed to tumor xenografts in a CD44 expression-dependent manner. Conclusion: Novel discovery of aptamer CD44-Apt1 that can bind both CD44E and CD44s illustrates high potential as nanoprobe to deliver anti-cancer therapeutics.

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Anti-CD44 DNA Aptamers Selectively Target Cancer Cells

Cited by 14 publications

References 55 publications

CD44: A Multifunctional Mediator of Cancer Progression

CD44: A Multifunctional Mediator of Cancer Progression

Imaging of Clear Cell Renal Carcinoma with Immune Checkpoint Targeting Aptamer-Based Probe

Development of CD44E/s dual-targeting DNA aptamer as nanoprobe to deliver treatment in hepatocellular carcinoma

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