Journal of Biochemistry 2021 April 1 [Link]
Haruhiko Fujihira, Daisuke Takakura, Atsushi Matsuda, Masaaki Abe, Michiyo Miyazaki, Tomomi Nakagawa, Kazunori Kajino, Kaori Denda-Nagai, Miki Noji, Okio Hino, Tatsuro Irimura
Mesothelioma is a highly aggressive tumor associated with asbestos exposure and is histologically classified into three types: epithelioid-type, sarcomatoid-type, and biphasic-type. The prognosis of mesothelioma patients is poor and there is no effective molecular-targeting therapy as yet. ERC/mesothelin is a glycoprotein that is highly expressed on several types of cancers including epithelioid mesothelioma, but also expressed on normal mesothelial cells. This is a predicted reason why there is no clinically approved therapeutic antibody targeting ERC/mesothelin. In the present study, we focused on the differential glycosylation between ERC/mesothelin present on epithelioid mesothelioma and that on normal mesothelial cells and aimed to reveal a distinct feature of epithelioid mesothelioma cells. Lectin microarray analysis of ERC/mesothelin using cells and patient specimens showed significantly stronger binding of PHA-E4 lectin, which recognizes complex-type N-glycans having a so-called bisecting-GlcNAc structure, to ERC/mesothelin from epithelioid mesothelioma cells than that from normal mesothelial cells. Further, LC/MS analysis on ERC/mesothelin from epithelioid mesothelioma cells confirmed the presence of a bisecting-GlcNAc attached to Asn388 of ERC/mesothelin. These results suggest that this glycoproteome could serve as a potential target for the generation of a highly selective and safe therapeutic antibody for epithelioid mesothelioma.