Mrc2, also known as Endo180 and Type 2 mannose receptor C, is a constitutively recycling transmembrane receptor belonging to the mannose receptor family. It is involved in various biological processes. In the context of the cell, it has been linked to promoting cell migration signaling pathway and invasion. It may also play a role in antigen presentation and process in certain cell types [2,4,5].

In a sarcoma tumor xenograft model, an anti-Endo180 monoclonal antibody-drug conjugate (ADC) showed on-target cytotoxicity, leading to tumor regression and impairment of metastatic colonization, while mice with an Mrc2 genetic deletion had no phenotype, suggesting potential for an Endo180-ADC as a sarcoma treatment [1]. In diabetic nephropathy, knockdown of Mrc2 in mouse mesangial cells inhibited cell proliferation and induced apoptosis, indicating Mrc2 may be a therapeutic target [2]. A rare missense variant in Mrc2 was associated with familial supraventricular tachycardia and Wolff-Parkinson-White syndrome in humans, and Mrc2 knock-in mice had an increased incidence of reentrant SVT and bypass tract formation [3].

In summary, Mrc2 is a multifunctional receptor. Studies using gene knockout or knock-in mouse models have revealed its role in diseases such as sarcoma, diabetic nephropathy, and cardiac arrhythmias. These findings highlight its potential as a therapeutic target in these disease areas.

References:

1. Evans, Rachel J, Perkins, Douglas W, Selfe, Joanna, Schipper, Koen, Isacke, Clare M. . Endo180 (MRC2) Antibody-Drug Conjugate for the Treatment of Sarcoma. In Molecular cancer therapeutics, 22, 240-253. doi:10.1158/1535-7163.MCT-22-0312. https://pubmed.ncbi.nlm.nih.gov/36399638/

2. Li, Lanlan, Chen, Xin, Zhang, Henglu, Wang, Min, Lu, Weiping. 2021. MRC2 Promotes Proliferation and Inhibits Apoptosis of Diabetic Nephropathy. In Analytical cellular pathology (Amsterdam), 2021, 6619870. doi:10.1155/2021/6619870. https://pubmed.ncbi.nlm.nih.gov/34012764/

3. Potter, Adam S, Miyake, Christina Y, Gonzaga-Jauregui, Claudia, Lalani, Seema R, Wehrens, Xander H T. 2024. Rare Variant in MRC2 Associated With Familial Supraventricular Tachycardia and Wolff-Parkinson-White Syndrome. In Circulation. Genomic and precision medicine, 17, e004614. doi:10.1161/CIRCGEN.124.004614. https://pubmed.ncbi.nlm.nih.gov/38953222/

4. Gai, Xiaohong, Tu, Kangsheng, Lu, Zhongtang, Zheng, Xin. 2014. MRC2 expression correlates with TGFβ1 and survival in hepatocellular carcinoma. In International journal of molecular sciences, 15, 15011-25. doi:10.3390/ijms150915011. https://pubmed.ncbi.nlm.nih.gov/25162823/

5. Wang, Wenhao, Li, Tiewen, Xie, Zhiwen, Ruan, Yuan, Han, Bangmin. 2024. Integrating single-cell and bulk RNA sequencing data unveils antigen presentation and process-related CAFS and establishes a predictive signature in prostate cancer. In Journal of translational medicine, 22, 57. doi:10.1186/s12967-023-04807-y. https://pubmed.ncbi.nlm.nih.gov/38221616/