Heparan sulfate analogues regulate tumor-derived exosome formation that attenuates exosome functions in tumor processes.

Abstract

Heparan sulfate (HS) is involved in many biological activities, including the biogenesis and uptake of exosomes, which are related to the occurrence and development of tumors. This study investigated the role of HS analogues (heparin, low molecular weight heparin, and 6-O-desulfated heparin) in modulating exosome secretion, composition and functions. Exosomes derived from B16F10 cells exposed to different HS analogues were isolated and characterized by TEM, western blotting and Nanosight analyses. The number, size and protein cargo of exosomes secreted by HS analogues-induced B16F10 cells were detected. The findings indicated the reduced tumor-derived exosome secretion and protein cargo as reflected by lower levels of CD63, TSG101, heparinase and IL-6 in exosomes derived from heparin-induced B16F10 cells as compared with 6-O-desulfated heparin-induced tumor cells. Further functional assays demonstrated that exosomes from tumor cells exposed to heparin weakened tumor proliferation, migration and invasion most significantly among various exosomes derived from B16F10 cells treated with different HS analogues. Moreover, the sulfate group at 6-O position of heparan sulfate has been proved to play an important role in tumor-derived exosome formation and functions. This study suggested a vital view to develop more specific and efficient HS-based strategies in cancer treatment for targeting tumor-derived exosomes.

• Authors: Xiaotao Wu, Mingzhu Kang, Danhui Wang, Min Zhu, Yiwei Hu, Yan Zhang, Chao Deng, Jinghua Chen, Liping Teng
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 187 Pg. 481-491 (Sep 30 2021) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 34298051 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Antineoplastic Agents
• Cd63 protein, mouse
• DNA-Binding Proteins
• Endosomal Sorting Complexes Required for Transport
• Heparin, Low-Molecular-Weight
• Interleukin-6
• Tetraspanin 30
• Transcription Factors
• Tsg101 protein
• heparin, O-desulfated
• interleukin-6, mouse
• Heparin
• Heparin Lyase

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• DNA-Binding Proteins (metabolism)
• Endosomal Sorting Complexes Required for Transport (metabolism)
• Exosomes (drug effects, metabolism, ultrastructure)
• Heparin (analogs & derivatives, pharmacology)
• Heparin Lyase (metabolism)
• Heparin, Low-Molecular-Weight (pharmacology)
• Interleukin-6 (metabolism)
• Melanoma, Experimental (drug therapy, metabolism, ultrastructure)
• Mice
• Neoplasm Invasiveness
• Skin Neoplasms (drug therapy, metabolism, ultrastructure)
• Tetraspanin 30 (metabolism)
• Transcription Factors (metabolism)