Cd248, also known as endosialin or tumor endothelial marker-1 (TEM-1), is a type 1 transmembrane glycoprotein expressed on activated mesenchymal cells. It functions during embryo development and is highly expressed in tumors and some fibrotic diseases, while being at low levels in adult tissues. Cd248 is involved in multiple pathways, such as the Wnt/β -catenin signaling pathway, and plays a significant role in angiogenesis, tumor growth, and fibrosis [2,5]. Gene knockout models are valuable for studying its functions.

In orthotopic lung cancer transplantation models, Cd248 -deficient (Cd248LacZ/LacZ) mice showed reduced tumor volume, vessel and pericyte density, and tumor vessel functionality compared to wild-type or haploinsufficient mice. Cd248 in pericytes derepresses Wnt signaling, upregulates angiogenic factors OPN and SERPINE1, and promotes angiogenesis and lung cancer growth. Administration of a β -catenin inhibitor in Cd248+/LacZ mice mimicked the effect of Cd248 loss, blocking the growth of transplanted lung tumor cells [1]. In a fibroblast-specific Cd248 gene knockout mouse model for non-small cell lung cancer (NSCLC), Cd248 knockout mice had a reduced ability to develop tumor lung metastasis. CD248+ cancer-associated fibroblasts (CAFs) activate the Hippo pathway, induce CTGF expression, facilitate the collagen I milieu of the stromal matrix, and promote NSCLC metastasis [4]. In diabetic kidney disease, Cd248 knockout ameliorated DKD-associated glomerular dysfunction and reversed maladaptive unfolded protein response signaling [3].

In conclusion, Cd248 is crucial in various biological processes and disease conditions. Through gene knockout mouse models, its role in promoting tumor growth and metastasis in lung cancer, and its contribution to diabetic kidney disease and pathologic scarring have been revealed. These findings suggest that Cd248 could be a potential therapeutic target for these diseases.