Chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes

Oncotarget
Anurag PurushothamanRobert Z Orlowski

Abstract

Tumor cells produce and utilize exosomes to promote tumor growth and metastasis. Tumor-cell-derived exosomes deliver cargos that partially mimic the contents of the parent cell to nearby or distant normal or abnormal cells, thereby reprogramming the recipient cells to support tumor progression. Mechanisms by which tumor-derived exosomes subserve the tumor are under intense investigation. Here we demonstrate a critical role of the chondroitin sulfate proteoglycan serglycin in regulating the protein cargo and functions of myeloma cell-derived exosomes. Previous studies have shown that serglycin, the only known intracellular proteoglycan, functions mainly in the storage of basically charged components within the intracellular granules/vesicles via serglycin's densely clustered, negatively charged glycosaminoglycan chains. Here we demonstrate that serglycin plays a critical role in the protein cargo loading of tumor-derived exosomes. Serglycin was detected in exosomes derived from cell culture supernatants of human myeloma cell lines and serum of myeloma patients. Mass spectrometry analysis of exosomal proteins identified significantly fewer protein components within exosomes derived from serglycin-knockdown myeloma cells than with...Continue Reading

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Citations

Aug 28, 2020·Cells·Sierra A WalkerJoy Wolfram
Nov 9, 2019·International Journal of Molecular Sciences·Tünde SzatmáriKatalin Lumniczky
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Apr 17, 2020·Signal Transduction and Targeted Therapy·Jawad FaresYoussef Fares
Sep 12, 2018·Chemical Reviews·Nikos K KaramanosRenato V Iozzo

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Methods Mentioned

BETA
transmission electron microscopy
gene
sulfotransferase
electron microscopy

Software Mentioned

ZetaView
DAVID ( Database for Annotation , Visualization and Integrated...
DAVID

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