Thbs2, also known as thrombospondin 2, is a secreted extracellular matrix protein. It plays crucial roles in various biological processes such as angiogenesis, tissue remodeling, and inflammation [4]. It is involved in multiple signaling pathways, including the MAPK, Notch, Wnt/β -catenin, and PI3K/AKT pathways, which are essential for cell growth, adhesion, migration, and epithelial-mesenchymal transition (EMT) [1,3,4,5,6].

In pancreatic ductal adenocarcinoma (PDAC), genetically engineered mouse models revealed that cancer cell-secreted TGF-β1 activates cancer-associated fibroblasts (CAFs) to induce Thbs2 expression via the p-Smad2/3 pathway. CAF-derived Thbs2 then binds to integrin αvβ3/CD36 on PDAC cells, activating the MAPK pathway to promote tumor growth and adhesion [1].

In early-stage lung adenocarcinoma, multi-omic analyses identified Thbs2 as a tumor size-independent biomarker. Thbs2+ CAFs promoted tumor aggressiveness, and Thbs2 recombinant protein suppressed T cell proliferation and promoted tumor growth and distant micro-metastasis in vivo [2].

In colorectal cancer, Thbs2+ CAFs promoted oxaliplatin resistance by interacting with malignant cells via the collagen pathway, specifically through COL8A1-mediated activation of the PI3K-AKT signaling pathway and promotion of EMT [3].

In gastric cancer, Thbs2 promoted tumor progression and stemness through the Notch signaling pathway, and down-regulation of Thbs2 impaired tumorigenesis and liver metastasis in nude mice [4].

In another study on colorectal cancer, the lncRNA RP11-417E7.1 promoted Thbs2 transcription, which activated the Wnt/β-catenin signaling pathway and facilitated exosome-mediated M2 macrophage polarization to promote metastasis in a mouse model [5].

In conclusion, Thbs2 is involved in multiple biological processes and is crucial in various cancer-related disease conditions. Studies using mouse models, such as genetically engineered mouse models and xenograft models, have significantly contributed to understanding the role of Thbs2 in cancer progression, metastasis, and drug resistance, providing potential therapeutic targets for these diseases.