Serum and urinary levels of CD222 in cancer: origin and diagnostic value

The mannose 6-phosphate/insulin-like growth factor 2 receptor (CD222, M6P/IGF2R) is a multifunctional transmembrane type I receptor, mostly localized intracellularly, less on the surface of all types of mammalian cells. It is known both to transport lysosomal enzymes through their mannose 6-phosphate moieties and to internalize extracellular ligands like insulin-like growth factor 2 or plasminogen. CD222 is involved in regulation of cell proliferation, migration, T cell activation, and apoptosis. Soluble CD222 has been found in higher concentrations in sera of liver disease patients. In this study, we analysed the level of CD222 present in body fluids, namely in serum and urine, of cancer patients. We found significantly elevated levels of soluble CD222 in sera of cancer patients compared to healthy controls irrespective of the type of disease. The urine CD222 levels were increased specifically in breast cancer and multiple myeloma. In contrast to serum, CD222 was present within CD222-positive exosomes in urine pointing to different origins of CD222 present in various human body fluids. Based on this work, we propose serum soluble CD222 as a general biomarker for tumorigenesis.