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Biology subjects

Kuwahara, R.

Publications and source records attributed to Kuwahara, R..

2 recordsLinked to original sources

Bimolecule detection for Extracellular Vesicle Screening

Extracellular vesicle (EV) has been investigated for use in clinical testing in recent years. Specific EV surface proteins provide distinguishing characteristics, but are insufficient for more detailed classification of EVs. Here, we suggest a novel "Bimolecular surface antigen expressed in EV" (BiEV) as a potential indicator for more efficient EV screening. A BiEV can be identified using a previously developed method, enzyme-mediated activation of radical sources, to label the components proximal (within 20 nm) to a given molecule. We examined the screening of cancer cell-secreted EV (cEV) included in serum EVs from a model mouse for lung cancer. The cEV-specific BiEVs were first identified by through a comparison of serum EVs from wild-type and lung cancer mice, showing that the CHL1-SLC4A1 bimolecule was a significant candidate for cEV-specific BiEV. Enzyme-linked immunosorbent assay quantification of CHL1-SLC4A1 BiEV appeared to suggest a potential for cancer screening of these mice. Using the same protocols, we found that CHL1-caspase 14 BiEV was significantly elevated in lung cancer patients compared with healthy persons. A BiEV strategy may be able to make a contribution to more effective EV screening, resulting in novel biological and clinical applications.

biochemistry↗

Proximity proteomics identifies cancer cell membrane cis-molecular complex as a potential cancer target

Cancer-specific antigens expressed in the cell membrane have been used as targets for several molecular targeted strategies in recent years with remarkable success. To develop more effective cancer treatments, novel targets and strategies for targeted therapies are needed. Here, we examined the cancer cell membrane-resident \"cis-bimolecular complex\" as a possible cancer target (cis-bimolecular cancer target: BiCAT) using proximity proteomics, a technique that has attracted attention in recent years. BiCATs were detected using a previously developed method, termed the enzyme-mediated activation of radical source (EMARS), to label the components proximal to a given cell membrane molecule. EMARS analysis identified some BiCATs, such as close homolog of L1 (CHL1), fibroblast growth factor 3 (FGFR3) and 2 integrin, which are commonly expressed in mouse primary lung cancer cells and human lung squamous cell carcinoma cells. Analysis of cancer specimens from 55 lung cancer patients revealed that approximately half of patients were positive for these BiCATs. In vitro simulation of effective drug combinations used for multiple drug treatment strategy was performed using reagents targeted to BiCAT molecules. The combination treatment based on BiCAT information moderately suppressed cancer cell proliferation compared with single administration, suggesting that the information about BiCATs in cancer cells is profitable for the appropriate selection of the combination among molecular targeted reagents. Thus, BiCAT has the possibility to make a contribution to several molecular targeted strategies in future.

biochemistry↗