Emmprin, released as a microvesicle in epithelioid sarcoma, interacts with fibroblasts

Aoki,Mikiko; Koga,Kaori; Hamasaki,Makoto; Egawa,Nagayasu; Nabeshima,Kazuki

doi:10.3892/ijo.2017.3986

Emmprin, released as a microvesicle in epithelioid sarcoma, interacts with fibroblasts

Authors:
- Mikiko Aoki
- Kaori Koga
- Makoto Hamasaki
- Nagayasu Egawa
- Kazuki Nabeshima
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Affiliations: Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
Published online on: May 8, 2017 https://doi.org/10.3892/ijo.2017.3986
Pages: 2229-2235

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Abstract

Emmprin (extracellular matrix metalloproteinase inducer, CD147) is a glycosylated transmembrane protein, consisting of two immunoglobulin domains, that stimulates the production of matrix metalloproteinases (MMPs) by tumor-associated fibroblasts. These effects play important roles in tumor invasion and metastasis. However, the precise mechanisms by which emmprin acts on fibroblasts have not been fully elucidated, especially in sarcoma cells. Previously, we demonstrated that emmprin, expressed in conditioned medium collected from the epithelioid sarcoma cell line (FU-EPS-1), stimulates MMP-2 production via interactions with fibroblasts. In this study, we used microvesicles derived from sarcoma cells, and determined whether emmprin exists in the microvesicles, which enhance the production of MMP-2 via fibroblasts. Microvesicles released from FU-EPS-1 cells were shown to contain full-length emmprin, identified as a 45-kDa protein characterized by polylactosamine glycosylation. Microvesicles collected from FU-EPS-1 cells transfected with emmprin-specific siRNA or transduced with shRNA displayed significantly reduced MMP-2 production by fibroblasts compared with those from control-transfected cells. Our findings show that emmprin is released through microvesicle shedding in sarcoma cells, and emmprin in microvesicles regulates MMP-2 production by influencing the activity of fibroblasts located at sites distant from the tumor cells.

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