Anti-angiogenic and anti-tumoral properties of CXCL9-derived glycosaminoglycan-binding peptides

Cancer progression leading to metastasis is a major cause of cancer-associated death. Over the years, the important role of glycosaminoglycans/proteoglycans in tumor progression has been acknowledged and more information on their specific roles therein is being elucidated. Glycosaminoglycans/proteoglycans are important interaction partners of proteins via which they mediate a lot of different cellular processes. The role of chemotactic cytokines or chemokines herein has been acknowlegded and chemokine-targeting drugs have been/are being developed. Important binding partners of chemokines are glycosaminoglycans (GAGs) present on proteoglycans on almost all cells. Aside from chemokines, GAGs also mediate the function of other signaling molecules, such as growth factors. A well-studied example of chemokine-glycosaminoglycan interaction is where a chemokine concentration gradient on the endothelium serves as a signpost for transendothelial leukocyte migration (e.g. neutrophil) in lymph nodes or inflamed tissues. Targeting this GAG-chemokine interaction is an alternative approach to interfere with chemokine function and has been shown to be effective in blocking chemokine-mediated neutrophil recruitment and subsequent inflammatory reactions. However, knowledge on the role of GAGs in the intravasation and extravasation of tumor cells, which are essential to the metastatic process, is very limited. Using chemokine-derived peptides that bind GAGs with high affinity and interfering with the GAG-chemokine interaction, we want to investigate the role of this interaction in various aspects of tumor progression.

Publication year:2022

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