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Aptamer-based approaches for in vitro molecular detection of cancer.

ABSTRACT: Cancer is typically associated with abnormal production of various tumor-specific molecules known as tumor markers. Probing these markers by utilizing efficient approaches could be beneficial for cancer diagnosis. The current widely-used biorecognition probes, antibodies, suffer from some undeniable shortcomings. Fortunately, novel oligonucleotide-based molecular probes named aptamers are being emerged as alternative detection tools with distinctive advantages compared to antibodies. All of the existing strategies in cancer diagnostics, including those of in vitro detection, can potentially implement aptamers as the detecting moiety. Several studies have been performed in the field of in vitro cancer detection over the last decade. In order to direct future studies, it is necessary to comprehensively summarize and review the current status of the field. Most previous studies involve only a few cancer diagnostic strategies. Here, we thoroughly review recent significant advances on the applications of aptamer in various in vitro detection strategies. Furthermore, we will discuss the status of diagnostic aptamers in clinical trials.

SUBMITTER: Bakhtiari H

PROVIDER: S-EPMC7306249 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Aptamer-based approaches for <i>in vitro</i> molecular detection of cancer.

Bakhtiari Hadi H Palizban Abbas Ali AA Khanahmad Hossein H Mofid Mohammad Reza MR

Research in pharmaceutical sciences 20200401 2

Cancer is typically associated with abnormal production of various tumor-specific molecules known as tumor markers. Probing these markers by utilizing efficient approaches could be beneficial for cancer diagnosis. The current widely-used biorecognition probes, antibodies, suffer from some undeniable shortcomings. Fortunately, novel oligonucleotide-based molecular probes named aptamers are being emerged as alternative detection tools with distinctive advantages compared to antibodies. All of the ...[more]

PMID: 32582351

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Project description:Molecular subtyping of breast cancer is of considerable interest owing to its potential for personalized therapy and prognosis. However, current methodologies cannot be used for precise subtyping, thereby posing a challenge in clinical practice. The aim of the present study is to develop a cell-specific single-stranded DNA (ssDNA) aptamer-based fluorescence probe for molecular subtyping of breast cancer. Methods: Cell-SELEX method was utilized to select DNA aptamers. Flow cytometry and confocal microscopy were used to study the specificity, binding affinity, temperature effect on the binding ability and target type analysis of the aptamers. In vitro and in vivo fluorescence imaging were used to distinguish the molecular subtypes of breast cancer cells, tissue sections and tumor-bearing mice. Results: Six SK-BR-3 breast cancer cell-specific ssDNA aptamers were evolved after successive in vitro selection over 21 rounds by Cell-SELEX. The Kd values of the selected aptamers were all in the low-nanomolar range, among which aptamer sk6 showed the lowest Kd of 0.61 ± 0.14 nM. Then, a truncated aptamer-based probe, sk6Ea, with only 53 nt and high specificity and binding affinity to the target cells was obtained. This aptamer-based probe was able to 1) differentiate SK-BR-3, MDA-MB-231, and MCF-7 breast cancer cells, as well as distinguish breast cancer cells from MCF-10A normal human mammary epithelial cells; 2) distinguish HER2-enriched breast cancer tissues from Luminal A, Luminal B, triple-negative breast cancer tissues, and adjacent normal breast tissues (ANBTs) in vitro; and 3) distinguish xenografts of SK-BR-3 tumor-bearing mice from those of MDA-MB-231 and MCF-7 tumor-bearing mice within 30 min in vivo. Conclusion: The results suggest that the aptamer-based probe is a powerful tool for fast and highly sensitive subtyping of breast cancer both in vitro and in vivo and is also very promising for the identification, diagnosis, and targeted therapy of breast cancer molecular subtypes.

Project description:BackgroundThyroid cancer, as with other types of cancer, is dependent on angiogenesis for its continued growth and development. Interestingly, estrogen has been shown to contribute to thyroid cancer aggressiveness in vitro, which is in full support of the observed increased incidence of thyroid cancer in women over men. Provided that estrogen has been observed to contribute to increased angiogenesis of estrogen responsive breast cancer, it is conceivable to speculate that estrogen also contributes to angiogenesis of estrogen responsive thyroid cancer.MethodsIn this study, three human thyroid cancer cells (B-CPAP, CGTH-W-1, ML-1) were treated with estrogen alone or estrogen and anti-estrogens (fulvestrant and 3,3'-diindolylmethane, a natural dietary compound) for 24 hours. The cell culture media was then added to human umbilical vein endothelial cell (HUVECs) and assayed for angiogenesis associated events. Vascular endothelial growth factor (VEGF) levels were also quantified in the conditioned media so as to evaluate if it is a key player involved in these observations.ResultsConditioned medium from estrogen treated thyroid cancer cells enhanced phenotypical changes (proliferation, migration and tubulogenesis) of endothelial cells typically observed during angiogenesis. These phenotypic changes observed in HUVECs were determined to be modulated by estrogen induced secretion of VEGF by the cancer cells. Lastly, we show that VEGF secretion was inhibited by the anti-estrogens, fulvestrant and 3,3'-diindolylmethane, which resulted in diminished angiogenesis associated events in HUVECs.ConclusionOur data establishes estrogen as being a key regulator of VEGF secretion/expression in thyroid cells which enhances the process of angiogenesis in thyroid cancer. These findings also suggest the clinical utility of anti-estrogens as anti-angiogenic compounds to be used as a therapeutic means to treat thyroid cancer. We also observed that 3,3'-diindolylmethane is a promising naturally occurring anti-estrogen which can be used as a part of therapeutic regimen to treat thyroid cancer.

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Aptamer-based approaches for in vitro molecular detection of cancer.

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Aptamer-based approaches for <i>in vitro</i> molecular detection of cancer.

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