3 years ago

The HDAC6 Inhibitor Tubacin Induces Release of CD133+ Extracellular Vesicles From Cancer Cells

The HDAC6 Inhibitor Tubacin Induces Release of CD133+ Extracellular Vesicles From Cancer Cells
Riccardo Alessandro, Tim C. Chang, Fabio Anzanello, Oscar B. Goodman, Aurelio Lorico, Germana Rappa, Maria A. Di Bella, Olivia S. Chao
Tumor-derived extracellular vesicles (EVs) are emerging as an important mode of intercellular communication, capable of transferring biologically active molecules that facilitate the malignant growth and metastatic process. CD133 (Prominin-1), a stem cell marker implicated in tumor initiation, differentiation and resistance to anti-cancer therapy, is reportedly associated with EVs in various types of cancer. However, little is known about the factors that regulate the release of these CD133+ EVs. Here, we report that the HDAC6 inhibitor tubacin promoted the extracellular release of CD133+ EVs from human FEMX-I metastatic melanoma and Caco-2 colorectal carcinoma cells, with a concomitant downregulation of intracellular CD133. This effect was specific for tubacin, as inhibition of HDAC6 deacetylase activity by another selective HDAC6 inhibitor, ACY-1215 or the pan-HDAC inhibitor trichostatin A (TSA), and knockdown of HDAC6 did not enhance the release of CD133+ EVs. The tubacin-induced EV release was associated with changes in cellular lipid composition, loss of clonogenic capacity and decrease in the ability to form multicellular aggregates. These findings indicate a novel potential anti-tumor mechanism for tubacin in CD133-expressing malignancies. J. Cell. Biochem. 118: 4414–4424, 2017. © 2017 Wiley Periodicals, Inc. Treatment of cancer cells with the HDAC6 inhibitor tubacin increased the release of extracellular vesicles (EVs) that contain CD133. This tubacin-induced EV release was associated with changes in cellular lipid composition, loss of clonogenic capacity, and decrease in the ability to form multicellular aggregates. These findings may constitute a potentially novel anti-cancer approach.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26095

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