eISSN: 1897-4309
ISSN: 1428-2526
Contemporary Oncology/Współczesna Onkologia
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SCImago Journal & Country Rank
2/2018
vol. 22
 
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abstract:
Original paper

Interferon-α-induced cytoplasmic MxA structures in hepatoma Huh7 and primary endothelial cells

Deodate Davis, Huijuan Yuan, Yang-Ming Yang, Feng-Xia Liang, Pravin B. Sehgal

Contemp Oncol (Pozn) 2018; 22 (2): 86-94
Online publish date: 2018/06/01
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Aim of the study
Interferon (IFN)-α is now established as a treatment modality in various human cancers. The IFN-α-inducible human “myxovirus resistance protein A” (MxA) is a cytoplasmic dynamin-family large GTPase primarily characterized for its broad-spectrum antiviral activity and, more recently, for its anti-tumor and anti-metastasis effects. We characterized the association of IFN-α-induced MxA with cytoplasmic structures in human Huh7 cancer cells and in primary endothelial cells.

Material and methods
We re-evaluated the long-standing inference that MxA associated with the smooth ER using double-label immunofluorescence techniques and the ER structural protein RTN4 as a marker for smooth ER in IFN-α-treated cells. We also evaluated the relationship of exogenously expressed HA-MxA and GFP-MxA with mitochondria, and characterized cytoplasmic GFP-MxA structures using correlated light and electron microscopy (CLEM).

Results and conclusions
We discovered that IFN-α-induced endogenous MxA associated with variably-sized endosome-like and reticular cytoplasmic structures which were distinct from the ER. Thin-section EM studies of GFP-MxA expressing Huh7 cells showed that GFP-MxA formed variably-sized clusters of vesiculotubular elements to form endosome-like “MxA bodies”. Many of these clusters stretched out alongside cytoskeletal elements to give the appearance of a cytoplasmic “MxA reticulum”. This MxA meshwork was distinct from but adjacent to mitochondria. GFP-MxA expressing Huh7 cells showed reduced MitoTracker uptake and swollen mitochondria by thin-section EM. The new data identify cytoplasmic MxA structures as novel organelles, and suggest cross-talk between MxA structures and mitochondria that might account for the increased anti-tumoral efficacy of IFN-α combined with ligands that activate other pattern-sensing receptor pathways.

keywords:

interferons, myxovirus resistance protein A, dynamin-family GTPase, MxA bodies, MxA reticulum, mitochondrial function, correlated light and electron microscopy (CLEM)

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