Aptamer Targets Triple-Negative Breast Cancer through Specific Binding to Surface CD49c.
Quanyuan WanZihua ZengJianjun QiYingxin ZhaoXiaohui LiuZhenghu ChenHaijun ZhouYouli ZuPublished in: Cancers (2022)
Although targeted cancer therapy can induce higher therapeutic efficacy and cause fewer side effects in patients, the lack of targetable biomarkers on triple-negative breast cancer (TNBC) cells limits the development of targeted therapies by antibody technology. Therefore, we investigated an alternative approach to target TNBC by using the PDGC21T aptamer, which selectively binds to poorly differentiated carcinoma cells and tumor tissues, although the cellular target is still unknown. We found that synthetic aptamer probes specifically bound cultured TNBC cells in vitro and selectively targeted TNBC xenografts in vivo. Subsequently, to identify the target molecule on TNBC cells, we performed aptamer-mediated immunoprecipitation in lysed cell membranes followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Sequencing analysis revealed a highly conserved peptide sequence consistent with the cell surface protein CD49c (integrin α3). For target validation, we stained cultured TNBC and non-TNBC cells with an aptamer probe or a CD49c antibody and found similar cell staining patterns. Finally, competition cell-binding assays using both aptamer and anti-CD49c antibody revealed that CD49c is the biomarker targeted by the PDGC21T aptamer on TNBC cells. Our findings provide a molecular foundation for the development of targeted TNBC therapy using the PDGC21T aptamer as a targeting ligand.
Keyphrases
- induced apoptosis
- cancer therapy
- gold nanoparticles
- single cell
- cell cycle arrest
- sensitive detection
- liquid chromatography tandem mass spectrometry
- cell therapy
- endoplasmic reticulum stress
- oxidative stress
- label free
- drug delivery
- end stage renal disease
- small molecule
- ejection fraction
- ms ms
- cell proliferation
- high throughput
- binding protein
- high resolution
- mass spectrometry
- peritoneal dialysis
- solid phase extraction
- patient reported outcomes