PRSS2, also known as serine protease 2, is a serine protease that has significant implications in multiple biological processes and diseases. It is involved in pathways related to tumor microenvironment regulation and cell migration and invasion. Trypsinogen, which includes PRSS2, is linked to pancreatitis risk through a gene dosage effect, highlighting its importance in pancreatic health [3].

In cancer research, PRSS2 has been shown to play detrimental roles. In gastric cancer, it promotes cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) [2,4,5]. High serum levels of PRSS2 in gastric cancer patients are associated with lymphatic metastasis and TNM stage, and it is positively correlated with serum MMP-9 level [2]. In the tumor microenvironment, PRSS2 remodels it via repression of Tsp-1, not through its enzymatic activity but by binding to LRP1, thus stimulating tumor growth and progression [1]. Regarding pancreatitis, genetic and transgenic studies suggest that increased trypsinogen gene dosage, including PRSS2, is correlated with pancreatitis risk, though no specific KO/CKO mouse model details were given in the references [3].

In conclusion, PRSS2 is a key serine protease involved in tumor-related processes such as growth, metastasis, and tumor microenvironment remodeling, as well as being associated with pancreatitis risk. Model-based research, especially in the context of cancer, has revealed its important roles in these disease areas, providing potential targets for therapeutic intervention.

References:

1. Sui, Lufei, Wang, Suming, Ganguly, Debolina, Akslen, Lars A, Watnick, Randolph S. 2022. PRSS2 remodels the tumor microenvironment via repression of Tsp1 to stimulate tumor growth and progression. In Nature communications, 13, 7959. doi:10.1038/s41467-022-35649-9. https://pubmed.ncbi.nlm.nih.gov/36575174/

2. Wang, Fei, Yi, Jianfeng, Chen, Yu, Feng, Shichun, Zhou, Xiaojun. 2023. PRSS2 regulates EMT and metastasis via MMP-9 in gastric cancer. In Acta histochemica, 125, 152071. doi:10.1016/j.acthis.2023.152071. https://pubmed.ncbi.nlm.nih.gov/37331089/

3. Zou, Wen-Bin, Cooper, David N, Masson, Emmanuelle, Férec, Claude, Chen, Jian-Min. 2022. Trypsinogen (PRSS1 and PRSS2) gene dosage correlates with pancreatitis risk across genetic and transgenic studies: a systematic review and re-analysis. In Human genetics, 141, 1327-1338. doi:10.1007/s00439-022-02436-x. https://pubmed.ncbi.nlm.nih.gov/35089416/

4. Chen, Yu, Wang, Biling, Zhao, Zihao, Li, Ming, Wang, Fei. 2022. PRSS2 overexpression relates to poor prognosis and promotes proliferation, migration and invasion in gastric cancer. In Tissue & cell, 79, 101949. doi:10.1016/j.tice.2022.101949. https://pubmed.ncbi.nlm.nih.gov/36240716/

5. Qin, Haifeng, Zhang, Shushu, Shen, Linling, Gao, Guangyu, Wang, Hui. 2023. High expression of serine protease 2 (PRSS2) associated with invasion, metastasis, and proliferation in gastric cancer. In Aging, 15, 2473-2484. doi:10.18632/aging.204604. https://pubmed.ncbi.nlm.nih.gov/37022096/