CCL21 and neoplasm: This occurred through distinct roles served by two forms of lymphatic endothelial HS: (1) Lymphatic-secreted HS (presented on proteoglycans in lymphatic endothelial conditioned medium), which appeared to serve as a soluble co-receptor for CCL21-CCR7 association and migration signaling on tumor cells; and (2) Lymphatic cell-surface HS (displayed on lymphatic membrane-bound proteoglycans), which appears to concentrate CCL21 on the lymph endothelium, and thereby serves as a means by which lymphatic vascular chemokine gradients may be regulated in vivo.