Universität zu Köln

Zhao, Jiangang, Schlosser, Hans A., Wang, Zhefang, Qin, Jie, Li, Jiahui, Popp, Felix, Popp, Marie Christine, Alakus, Hakan, Chon, Seung-Hun ORCID: 0000-0002-8923-6428, Hansen, Hinrich P., Neiss, Wolfram E., Jauch, Karl-Walter, Bruns, Christiane J. and Zhao, Yue ORCID: 0000-0002-6790-3402 (2019). Tumor-Derived Extracellular Vesicles Inhibit Natural Killer Cell Function in Pancreatic Cancer. Cancers, 11 (6). BASEL: MDPI. ISSN 2072-6694

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Tumor-derived extracellular vesicles (EVs) induce pre-metastatic niche formation to promote metastasis. We isolated EVs from a highly-metastatic pancreatic cancer cell line and patient-derived primary cancer cells by ultracentrifugation. The protein content of EVs was analyzed by mass spectrometry. The effects of PDAC-derived EVs on natural kill (NK) cells were investigated by flow cytometry. The serum EVs' TGF- beta 1 levels were quantified by ELISA. We found that integrins were enriched in PDAC-derived EVs. The expression of NKG2D, CD107a, TNF-alpha, and INF-gamma in NK cells was significantly downregulated after co-culture with EVs. NK cells also exhibited decreased levels of CD71 and CD98, as well as impaired glucose uptake ability. In addition, NK cell cytotoxicity against pancreatic cancer stem cells was attenuated. Moreover, PDAC-derived EVs induced the phosphorylation of Smad2/3 in NK cells. Serum EVs' TGF- beta 1 was significantly increased in PDAC patients. Our findings emphasize the immunosuppressive role of PDAC-derived EVs and provide new insights into our understanding of NK cell dysfunction regarding pre-metastatic niche formation in PDAC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zhao, Jiangang UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlosser, Hans A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Zhefang UNSPECIFIED UNSPECIFIED UNSPECIFIED Qin, Jie UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Jiahui UNSPECIFIED UNSPECIFIED UNSPECIFIED Popp, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Popp, Marie Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Chon, Seung-Hun UNSPECIFIED orcid.org/0000-0002-8923-6428 UNSPECIFIED Hansen, Hinrich P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Neiss, Wolfram E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jauch, Karl-Walter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhao, Yue UNSPECIFIED orcid.org/0000-0002-6790-3402 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-138559
DOI:	10.3390/cancers11060874
Journal or Publication Title:	Cancers
Volume:	11
Number:	6
Date:	2019
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language METASTATIC NICHE FORMATION; NK CELLS; EXOSOMES; NKG2D; CYTOTOXICITY; DOCETAXEL; PHENOTYPE; HALLMARKS; NIVOLUMAB; DELIVERY Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13855