MSLN

MSLN Full Name

mesothelin

MSLN Introduction

Mesothelin (MSLN) is a cell-surface glycoprotein that is normally expressed on the mesothelial cells lining the pleura, peritoneum, and pericardium, but is aberrantly overexpressed in several cancers, most prominently mesothelioma, pancreatic adenocarcinoma, ovarian carcinoma, and lung adenocarcinoma. The protein is produced as a ~70 kDa precursor that is cleaved by furin to release a soluble megakaryocyte-potentiating factor and to leave a GPI-anchored mesothelin on the cell surface. The MSLN gene maps to chromosome 16p13.3 and gives rise to several splice variants with different membrane-anchoring properties.

Figure 1. The structure of MSLN.

Cell Adhesion, Migration, and Signaling on the Tumor Surface
GPI-anchored mesothelin localizes to lipid rafts on the cancer cell surface and binds CA125/MUC16 on the surface of mesothelial or tumor cells, mediating heterotypic cell adhesion that supports peritoneal and pleural metastatic spread. Through its interaction with MUC16 and with ERBB family receptors, mesothelin activates MAPK and PI3K signaling in tumor cells and may also engage NF-κB in macrophages that come into contact with mesothelin-bearing cancer cells. Cleavage of the precursor generates a shed form that can act as a decoy and may bind mesothelin-targeting antibodies, modulating therapeutic efficacy.

Cancer Immunotherapy Targeting
Mesothelin is one of the most actively pursued cell-surface targets in solid tumor immunotherapy, given its high expression on mesothelioma, pancreatic, ovarian, and certain lung cancers and its limited expression on normal tissues. Antibody-drug conjugates (e.g., anetumab ravtansine), chimeric antigen receptor T cells, T-cell engagers, and mesothelin-targeting vaccines are all in clinical development. Atezolizumab plus bevacizumab combinations are approved for hepatocellular carcinoma based in part on MSLN expression correlations, and MSLN-targeted antibody-drug conjugates have received accelerated FDA approval for platinum-resistant ovarian cancer.

Alternate Names for MSLN

MSLN; mesothelin; MPF; SMRP; CAK1 antigen; megakaryocyte potentiating factor; soluble MPF mesothelin related protein; pre-pro-megakaryocyte-potentiating factor;