In the present study, we demonstrate that sE-selectin functions as a signaling molecule in circulation with the ability to 1) enhance shear-resistant adhesion and migration of CD44+/high breast cancer cells (BCs) and leukocytes in an endothelial E-selectin independent fashion, 2) activate focal adhesion kinase (FAK), 3) promote homing of CD44+/high BCs to the lung, and 4) stimulate tumor growth and intratumoral infiltration of PBMCs. Here, SELE is linked to breast carcinoma.