Moreover, the effects of JAM-C on various physiological and pathological processes, including the self-renewal of leukemia-initiating cells and malignant behavior of melanoma and lung adenocarcinoma cells [16,33,34,35], might be at least in part attributed to the shedding of the JAM-C ectodomain and its accumulation in the extracellular matrix. Here, JAM3 is linked to leukemia.