CXCL3, a member of the C-X-C chemokine subfamily, acts as a potent chemoattractant for neutrophils, orchestrating leukocyte recruitment and migration, and triggering an inflammatory response. It exerts its functions mainly through interaction with its receptor CXCR2, activating signaling cascades such as ERK/MAPK, AKT, and JAK2/STAT3, which are involved in tumorigenesis [2]. Genetic models, like gene knockout (KO) mouse models, can be valuable for studying CXCL3's role in various biological processes.

In pancreatic ductal adenocarcinoma (PDAC), CXCL3, highly upregulated in IL-33-stimulated macrophages, promotes metastasis. Activation of the IL-33-ST2-MYC pathway leads to high CXCL3 production. CXCL3 activates CXCR2 in cancer-associated fibroblasts (CAFs), inducing a CAF-to-myoCAF transition and upregulating α-smooth muscle actin, with type III collagen being the adhesive molecule responsible for myoCAF-driven PDAC metastasis [1]. In osteoarthritis, TREM2 deficiency in mice enhances NF-κB signaling and CXCL3 expression, exacerbating joint inflammation, accelerating disease progression, increasing chondrocyte apoptosis, and inhibiting chondrocyte proliferation. Knocking down CXCL3 in TREM2-KO mice macrophages significantly inhibits the inflammatory response and promotes chondrocyte proliferation [3].

In conclusion, CXCL3 plays crucial roles in inflammation and tumor-related processes. Studies using KO mouse models in diseases like PDAC and osteoarthritis have revealed its impact on disease progression. Understanding CXCL3's functions provides insights into the mechanisms of these diseases, potentially leading to new therapeutic strategies targeting this molecule and its associated pathways.