Mesothelin isoform 2 (MSLN)

Mesothelin isoform 2 is a variant of the mesothelin protein, a cell surface glycoprotein highly expressed in various human cancers including mesothelioma, ovarian, and pancreatic adenocarcinomas, but with limited expression in normal tissues (mainly mesothelium)[1][3][6]. It plays a key role in cellular adhesion and tumor metastasis through interaction with cancer antigen CA-125 (MUC16). Structurally, mesothelin contains a rigid N-terminal and a flexible C-terminal region, with multiple N-glycosylation sites[1][2][3]. Mesothelin isoform 2 is specifically targeted by novel antibodies for cancer therapy; clinical strategies under investigation include monoclonal antibodies, antibody-drug conjugates, and CAR-T cells. Its restricted normal tissue distribution and upregulation in tumors make it an attractive target for therapeutic intervention, but clinical use is challenged by potential toxicity to mesothelial cells and difficulties related to protein shedding.

Other names

MesothelinPre-pro-megakaryocyte-potentiating factor (pre-pro-MPF)Megakaryocyte-potentiating factor (MPF)

Antibody-dependent cell-mediated cytotoxicity (ADCC); Blocking mesothelin-CA-125 interaction and preventing tumor metastasis[1][3]; Inhibition of mesothelin shedding (unique to some mAbs, e.g., 15B6)[1]