Cancer-Associated Glycoforms of Gelatinase B Exhibit a Decreased Level of Binding to Galectin-3

详细信息    查看全文

• 作者：Simon A. Fry ; Philippe E. Van den Steen ; Louise Royle ; Mark R. Wormald ; Anthony J. Leathem ; Ghislain Opdenakker ; James M. McDonnell ; Raymond A. Dwek ; Pauline M. Rudd
• 刊名：Biochemistry
• 出版年：2006
• 出版时间：December 26, 2006
• 年：2006
• 卷：45
• 期：51
• 页码：15249 - 15258
• 全文大小：585K
• 年卷期：v.45,no.51(December 26, 2006)
• ISSN：1520-4995

文摘

Gelatinase B (MMP-9) and galectin-3 are widely known to participate in tumor cell invasionand metastasis. Glycans derived from MMP-9 expressed in MCF-7 breast cancer and THP-1 myeloidleukemia cells were compared with those from MMP-9 expressed in natural neutrophils. The many O-linkedglycans of neutrophil gelatinase B presented a cluster of mainly galactosylated core II structures, 46% ofwhich were ligands for galectin-3; 11% contained two to three N-acetyllactosamine repeating units thatare high-affinity ligands for the lectin. The glycan epitopes thus provide MMP-9 with both high-affinityand (presumably) high-avidity interactions with galectin-3. In contrast, the O-glycans released from MMP-9expressed in MCF-7 and THP-1 cells were predominantly sialylated core I structures. Only 10% of MCF-7and THP-1 gelatinase B O-glycans were ligands for galectin-3 and contained only a maximum singleN-acetyllactosamine repeat. Consistent with the glycan analysis, surface plasmon resonance binding assaysindicated that the cancer-associated glycoforms of MMP-9 bound galectin-3 with an affinity and aviditysignificantly reduced compared with those of the natural neutrophil MMP-9. Galectin-3 exists as a multimerthat also binds laminin, providing a means of localizing neutrophil MMP-9 in the extracellular matrix(ECM). The analytical data presented here suggest that MMP-9 glycoforms secreted by tumor cells areunlikely to be tethered at the site of secretion, thus promoting more extensive cleavage of the ECM andproviding a rationale for the contribution that gelatinase B makes to cancer cell metastasis.