Granulin secreted by the food-borne liver fluke Opisthorchis viverrini promotes angiogenesis in human endothelial cells

Haugen, Brandon, Karinshak, Shannon E., Mann, Victoria H., Popratiloff, Anastas, Loukas, Alex, Brindley, Paul J., and Smout, Michael J. (2018) Granulin secreted by the food-borne liver fluke Opisthorchis viverrini promotes angiogenesis in human endothelial cells. Frontiers in Medicine, 5. 30.

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Abstract

The liver fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent countries in Southeast Asia. The adult developmental stage of the O. viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the liver fluke represent wounds that undergo protracted cycles of healing and re-injury during chronic infection, which can last for decades. Components of the excretory/secretory (ES) complement released by the worms capably drive proliferation of bile duct epithelial cells and are implicated in establishing the oncogenic milieu that leads to bile duct cancer, cholangiocarcinoma. An ES protein, the secreted granulin-like growth factor termed Ov-GRN-1, accelerates wound resolution in mice and in vitro. To investigate angiogenesis (blood vessel development) that may contribute to wound healing promoted by liver fluke granulin and, by implication, to carcinogenesis during chronic opisthorchiasis, we employed an in vitro tubule formation assay (TFA) where human umbilical vein endothelial cells were grown on gelled basement matrix. Ten and 40 nM Ov-GRN-1 significantly stimulated angiogenesis as monitored by cellular proliferation and by TFA in real time. This demonstration of potent angiogenic property of Ov-GRN-1 bolsters earlier reports on the therapeutic potential for chronic non-healing wounds of diabetics, tobacco users, and the elderly and, in addition, showcases another of the hallmark of cancer characteristic of this carcinogenic liver fluke.

Item ID: 57265
Item Type: Article (Research - C1)
ISSN: 2296-858X
Copyright Information: Copyright © 2018 Haugen, Karinshak, Mann, Popratiloff, Loukas, Brindley and Smout. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Funders: National Cancer Institute (NCI), National Institutes of Health (NIH)
Projects and Grants: NCI CA164719
Date Deposited: 28 Feb 2019 01:22
FoR Codes: 06 BIOLOGICAL SCIENCES > 0603 Evolutionary Biology > 060307 Host-Parasite Interactions @ 70%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060108 Protein Trafficking @ 30%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 50%
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