Mmp28, also known as epilysin, is a member of the matrix metalloproteinases (MMPs) family. MMPs are well-known for extracellular matrix remodelling, and Mmp28, as a secreted MMP, is involved in wound healing, immune system maturation, cell survival, migration, and embryogenesis [1]. It may play roles in neural crest-placode interactions during embryogenesis and is associated with multiple signalling pathways, such as MAPK/JNK, Notch3, which are crucial for its functions in various biological processes [2,3].

In murine models, Mmp28 -/- mice showed deficits in M2 macrophage polarization, leading to reduced fibrosis in bleomycin-induced lung injury, indicating that Mmp28 promotes M2 macrophage programming and fibrotic responses in the lung [4]. In pancreatic cancer, MMP28 promotes the malignant progression by recruiting M2-type tumor-associated macrophages through MAPK/JNK signaling pathway-dependent cytokine secretion [2]. In hepatocellular carcinoma, MMP28 promotes migration and invasion via Notch3 signaling [3]. In gastric cancer, overexpression of MMP28 in cell lines promoted tumor cell invasion in vitro and increased metastasis in vivo [5].

In conclusion, Mmp28 plays essential roles in processes like macrophage polarization, embryonic development, and is closely associated with the progression of multiple cancers including pancreatic, hepatocellular, and gastric cancer. Gene knockout models, especially in mice, have been instrumental in revealing these functions, highlighting Mmp28 as a potential therapeutic target for related diseases.

References:

1. Gouignard, Nadege, Theveneau, Eric, Saint-Jeannet, Jean-Pierre. 2020. Dynamic expression of MMP28 during cranial morphogenesis. In Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 375, 20190559. doi:10.1098/rstb.2019.0559. https://pubmed.ncbi.nlm.nih.gov/32829678/

2. Dong, Shi, Li, Xin, Chen, Zhou, Wang, Zhengfeng, Zhou, Wence. 2025. MMP28 recruits M2-type tumor-associated macrophages through MAPK/JNK signaling pathway-dependent cytokine secretion to promote the malignant progression of pancreatic cancer. In Journal of experimental & clinical cancer research : CR, 44, 60. doi:10.1186/s13046-025-03321-x. https://pubmed.ncbi.nlm.nih.gov/39972459/

3. Zhou, Jiangfan, Zheng, Xixi, Feng, Mei, Wang, Yilin, Jin, Jing. 2019. Upregulated MMP28 in Hepatocellular Carcinoma Promotes Metastasis via Notch3 Signaling and Predicts Unfavorable Prognosis. In International journal of biological sciences, 15, 812-825. doi:10.7150/ijbs.31335. https://pubmed.ncbi.nlm.nih.gov/30906212/

4. Gharib, Sina A, Johnston, Laura K, Huizar, Isham, Parks, William C, Manicone, Anne M. 2013. MMP28 promotes macrophage polarization toward M2 cells and augments pulmonary fibrosis. In Journal of leukocyte biology, 95, 9-18. doi:10.1189/jlb.1112587. https://pubmed.ncbi.nlm.nih.gov/23964118/

5. Jian, Pan, Yanfang, Tao, Zhuan, Zhou, Xueming, Zhu, Jian, Ni. 2011. MMP28 (epilysin) as a novel promoter of invasion and metastasis in gastric cancer. In BMC cancer, 11, 200. doi:10.1186/1471-2407-11-200. https://pubmed.ncbi.nlm.nih.gov/21615884/