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Sci Rep. 2017 Oct 16;7(1):13201. doi: 10.1038/s41598-017-13501-1.

Cell-surface major vault protein promotes cancer progression through harboring mesenchymal and intermediate circulating tumor cells in hepatocellular carcinomas.

Author information

1
Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul, Korea.
2
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
3
Department of Nanobiomedical Science, BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Korea.
4
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
5
Center for Colorectal Cancer, Research Institute and Hospital of National Cancer Center, Goyang-si, Korea.
6
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. oncorkim@skku.edu.
7
Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul, Korea. cjryu@sejong.ac.kr.

Abstract

Circulating tumor cells (CTCs) play a major role in the metastasis and recurrence of hepatocellular carcinoma (HCC). Here, we found that major vault protein (MVP) is expressed on the surface of HCC cells and further induced under stressful environments. MVP knockdown reduces cell proliferation and induces apoptosis in HCC cells. Treatment of HCC cells with anti-MVP antibody (α-MVP) recognizing cell-surface MVP (csMVP) inhibits cell proliferation, migration, and invasion. csMVP-positive HCC cells have a higher clonogenic survival than csMVP-negative HCC cells, and treatment of HCC cells with α-MVP inhibits clonogenic survival, suggesting that csMVP contributes to HCC cell survival, migration, and invasion. The function of csMVP is mediated through mTOR, FAK, ERK and Akt signaling pathways. csMVP-positive CTCs are detected in HCC patients (89.7%) but not in healthy donors, and the number of csMVP-positive CTCs is further increased in patients with metastatic cancers. csMVP is exclusively detectable in CTCs with mesenchymal phenotype or intermediate phenotype with neither epithelial nor mesenchymal markers, suggesting that csMVP-associated survival and metastatic potential harbor CTCs with nonepithelial phenotypes. The results suggest that csMVP promotes cancer progression and serves as a surface marker for mesenchymal and intermediate CTCs in patients with HCC and metastatic cancers.

PMID:
29038587
PMCID:
PMC5643512
DOI:
10.1038/s41598-017-13501-1
[Indexed for MEDLINE]
Free PMC Article

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