Soluble CD248 in the tumor microenvironment: From stromal byproduct to functional decoy

The tumor microenvironment is a rich source of soluble factors that regulate tumor growth and invasion. Among them, soluble CD248 (sCD248) has recently emerged as a potential modulator of tumor progression. CD248 is upregulated in cancer, predominantly expressed by perivascular cells and cancer-associated fibroblasts, but also by subsets of tumor cells in several types of cancer. Experimental studies have demonstrated that membrane-bound CD248 (mbCD248), present at the tumor cell surface, promotes migratory and invasive activities through interaction with extracellular matrix components. In contrast, emerging evidence indicates that sCD248 can interfere with this interaction, thus limiting tumor progression. Other hypothetical functions of sCD248 include interference with angiogenesis and immune modulation. This review highlights the importance of distinguishing mbCD248, which drives tumor progression at the tumor cell surface, from sCD248 within the tumor microenvironment. We propose that sCD248 is not merely a stromal byproduct but a functional decoy, with potential value as both a biomarker and a therapeutic tool.