Different CS/DS structures mediate diverse function during cancer development. The sulfation pattern of CS/DS in cancer differs from normal tissue. For example, 6-O-mono-sulfated disaccharides are accumulated in tumours compared to normal tissues, whereas 4-O-mono-sulfated disaccharides are reduced 70. During metastasis, CS/DS disaccharides sulfated at positions 4 and 6 (E units) present on the surface of cancer cells facilitate colonization of the lung and liver 71,72. The process might be mediated by the receptor RAGE, which is highly expressed in the lung 73. Another pro-metastatic activity of the E units on cancer cells could be a result of the capability to bind platelet P-selectin 49, resulting in the formation of tumour microemboli. These cell–platelet aggregates protect cancer cells against elimination by the immune system. IdoA in CS/DS is also known to mediate P-selectin binding. Two CS/DS structures containing IdoA (iB units or iD units), as isolated from marine animals, inhibit metastasis in a P-selectin-dependent manner in a metastatic tumour model 49. Several studies report that CS/DS structures mediate growth factor and chemokine binding. IdoA is essential for HGF-mediated binding and an
