Soluble CD146 serves as a marker of microvascular stress and promotes tumor invasionSoluble CD146 May Help Identify Cancer and Heart Stress

Soluble CD146 (sCD146) is a key circulating biomarker released from vascular endothelial cells via enzymatic cleavage under conditions of stress or activation.sCD146 not only dynamically reflects the integrity of the microvascular endothelial barrier but also profoundly drives the malignant progression of multisystem diseases through targeted interactions with its receptors (such as angiopoietin AMOT and VEGFR2). In malignant solid tumors, it accelerates tumor invasion and immune evasion by inducing epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) phenotypes; In cardiovascular diseases and early-life developmental abnormalities (such as bronchopulmonary dysplasia), it serves as a highly sensitive marker of tissue stasis and microvascular stress. However, the clinical application of sCD146 currently faces substantial translational hurdles: on the one hand, the lack of a standardized, cross-platform detection system and universally accepted clinical-pathological cutoff values hinders data interoperability across centers; on the other hand, its baseline expression exhibits heterogeneity in complex complications, and whether it serves as a “key mediator” of disease progression or a “bystander” of concomitant injury remains inconclusive in certain pathological states. In light of this, this review breaks down disciplinary barriers to systematically summarize the latest medical advances regarding sCD146 across oncology, cardiovascular, neuroimmunology, and reproductive development fields. It clarifies the core pathogenic mechanisms of sCD146 in different microenvironments, addresses practical challenges in clinical translation, and provides a solid theoretical foundation to advance sCD146 from a laboratory biomarker to a clinical precision diagnostic and therapeutic target.