Bgn, also known as biglycan, is an extracellular matrix proteoglycan. It can bind to transforming growth factor beta (TGF-β), regulating its free concentration, and is involved in pathways like extracellular matrix (ECM)-receptor interaction, focal adhesion, Wnt signaling, and VEGF signaling. Bgn is important in processes such as bone formation, tissue repair, and has implications in various diseases [2,4].

In gastric cancer, Bgn promotes tumor progression and the transformation of mesothelial cells into cancer-associated fibroblasts like cells (CAFLCs). CAFLCs-derived fibroblast activation protein (FAP) in turn facilitates the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of gastric cancer cells, forming a BGN/FAP-STAT3 positive feedback loop that contributes to peritoneal metastasis [1]. In colorectal cancer, Bgn positive cancer-associated fibroblasts (BGN + Fib) serve as a driver, and downregulation of Bgn in CAFs reduces CRC cell migration and proliferation [3]. In aortic stenosis, Bgn is a new endogenous agonist of TLR3, and Bgn -/-mice are protected against calcific aortic valve disease (CAVD) and display impaired bone formation [2].

In summary, Bgn is crucial for processes like bone formation and has significant implications in diseases such as gastric cancer, colorectal cancer, and aortic stenosis. The use of Bgn knockout mouse models has been instrumental in revealing its role in these disease conditions, providing insights into potential therapeutic targets and disease mechanisms [1,2,3].

References:

1. Wu, Haitao, Xiang, Zhenxian, Huang, Guoquan, Wang, Shuyi, Xiong, Bin. 2023. BGN/FAP/STAT3 positive feedback loop mediated mutual interaction between tumor cells and mesothelial cells contributes to peritoneal metastasis of gastric cancer. In International journal of biological sciences, 19, 465-483. doi:10.7150/ijbs.72218. https://pubmed.ncbi.nlm.nih.gov/36632455/

2. Gollmann-Tepeköylü, Can, Graber, Michael, Hirsch, Jakob, Tancevski, Ivan, Holfeld, Johannes. 2023. Toll-Like Receptor 3 Mediates Aortic Stenosis Through a Conserved Mechanism of Calcification. In Circulation, 147, 1518-1533. doi:10.1161/CIRCULATIONAHA.122.063481. https://pubmed.ncbi.nlm.nih.gov/37013819/

3. Hu, Shangshang, Xiao, Qianni, Gao, Rui, Pan, Yuqin, Wang, Shukui. 2024. Identification of BGN positive fibroblasts as a driving factor for colorectal cancer and development of its related prognostic model combined with machine learning. In BMC cancer, 24, 516. doi:10.1186/s12885-024-12251-4. https://pubmed.ncbi.nlm.nih.gov/38654221/

4. Cho, Sung Yoon, Bae, Jun-Seok, Kim, Nayoung K D, Park, Woong-Yang, Jin, Dong-Kyu. 2016. BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia. In American journal of human genetics, 98, 1243-1248. doi:10.1016/j.ajhg.2016.04.004. https://pubmed.ncbi.nlm.nih.gov/27236923/