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Cancer Lett. 2019 Jul 10;454:44-52. doi: 10.1016/j.canlet.2019.04.007. Epub 2019 Apr 10.

Mycoplasma infection promotes tumor progression via interaction of the mycoplasmal protein p37 and epithelial cell adhesion molecule in hepatocellular carcinoma.

Author information

1
Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul, South Korea.
2
Department of Pathology, College of Medicine, Hanyang University, Seoul, South Korea.
3
Department of Surgery, College of Medicine, Hanyang University, Seoul, South Korea; HY Indang Center of Regenerative Medicine and Stem Cell Research, South Korea.
4
Department of Radiology, College of Medicine, Hanyang University, Seoul, South Korea.
5
Department of Surgery, College of Medicine, Hanyang University, Seoul, South Korea. Electronic address: crane87@hanyang.ac.kr.
6
Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul, South Korea. Electronic address: cjryu@sejong.ac.kr.

Abstract

Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer death worldwide. To study how mycoplasma infection affects HCC progression, we investigated the characteristics of mycoplasma-infected tumor tissues and circulating tumor cells (CTCs) in HCC patients. The mycoplasmal membrane protein p37 showed significant correlations with higher histologic stages and vascular invasion and predicted poor disease-free survival of HCC patients. p37-positive CTCs were detected in 42 out of 47 HCC patients (89%). p37-positive circulating cells were also detected in 4 out of 10 healthy donors (40%), and all were epithelial cell adhesion molecule (EpCAM)-positive. In HCC patients, most of p37-negative CTCs (95%) showed intermediate phenotype with neither EpCAM nor vimentin expression, but p37-positive CTCs were EpCAM-positive (44%), vimentin-positive (32%), and both negative (24%), suggesting that EpCAM-positive CTCs are enriched with mycoplasma infection. Mycoplasma infection promoted migratory capacity of HCC cells with increased expression of EpCAM. Immunoprecipitation analysis revealed that p37 associates with EpCAM. The results suggest that mycoplasma infection promotes tumor progression in HCC patients via interaction of the mycoplasmal p37 and EpCAM.

KEYWORDS:

Circulating tumor cell; EpCAM; Hepatocellular carcinoma; Invasion and migration; Mycoplasmal p37 protein

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