Pfeiler, Susanne ORCID: 0000-0002-8591-6186, Thakur, Manovriti, Gruenauer, Petra, Megens, Remco T. A., Joshi, Urjita, Coletti, Raffaele, Samara, Verena, Mueller-Stoy, Geraldine, Ishikawa-Ankerhold, Hellen, Stark, Konstantin ORCID: 0000-0002-5369-8399, Klingl, Andreas, Froehlich, Thomas, Arnold, Georg J., Woermann, Sonja, Bruns, Christiane J., Alguel, Hana, Weber, Christian ORCID: 0000-0003-4610-8714, Massberg, Steffen and Engelmann, Bernd (2019). CD36-triggered cell invasion and persistent tissue colonization by tumor microvesicles during metastasis. Faseb J., 33 (2). S. 1860 - 1873. BETHESDA: FEDERATION AMER SOC EXP BIOL. ISSN 1530-6860

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Abstract

Tumor microvesicles are a peculiar type of extracellular vesicles that circulate in the blood of patients with metastatic cancer. The itineraries and immune cell interactions of tumor microvesicles during the intravascular and extravascular stages of metastasis are largely unknown. We found that the lipid receptor CD36 is a major mediator of the engulfment of pancreatic tumor microvesicles by myeloid immune cells in vitro and critically samples circulating tumor microvesicles by resident liver macrophages in mice in vivo. Direct nanoscopic imaging of individual tumor microvesicles shows that the microvesicles rapidly decay during engulfment whereby their cargo is targeted concomitantly to the plasma membrane and the cytoplasm excluding lysosomal compartments. CD36 also promotes internalization of blood cell (nontumor) microvesicles, which involves endolysosomal pathways. A portion of tumor microvesicles circulating in the liver microcirculation traverses the vessel wall in a CD36-dependent way. Extravasated microvesicles colonize distinct perivascular Ly6C(-) macrophages for at least 2 wk. Thus, the microvesicles are increasingly integrated into CD36-induced premetastatic cell clusters and enhance development of liver metastasis. Hence, promotion of metastasis by pancreatic tumor microvesicles is associated with CD36-regulated immune cell invasion and extravasation of microvesicles and persistent infiltration of specific tissue macrophages by microvesicle cargo.Pfeiler, S., Thakur, M., Grunauer, P., Megens, R. T. A., Joshi, U., Coletti, R., Samara, V., Muller-Stoy, G., Ishikawa-Ankerhold, H., Stark, K., Klingl, A., Frohlich, T., Arnold, G. J., Wormann, S., Bruns, C. J., Algul, H., Weber, C., Massberg, S., Engelmann, B. CD36-triggered cell invasion and persistent tissue colonization by tumor microvesicles during metastasis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Pfeiler, SusanneUNSPECIFIEDorcid.org/0000-0002-8591-6186UNSPECIFIED
Thakur, ManovritiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruenauer, PetraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Megens, Remco T. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Joshi, UrjitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coletti, RaffaeleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Samara, VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller-Stoy, GeraldineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ishikawa-Ankerhold, HellenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stark, KonstantinUNSPECIFIEDorcid.org/0000-0002-5369-8399UNSPECIFIED
Klingl, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Froehlich, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold, Georg J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woermann, SonjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, Christiane J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alguel, HanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, ChristianUNSPECIFIEDorcid.org/0000-0003-4610-8714UNSPECIFIED
Massberg, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engelmann, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-158210
DOI: 10.1096/fj.201800985R
Journal or Publication Title: Faseb J.
Volume: 33
Number: 2
Page Range: S. 1860 - 1873
Date: 2019
Publisher: FEDERATION AMER SOC EXP BIOL
Place of Publication: BETHESDA
ISSN: 1530-6860
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EXTRACELLULAR VESICLES; CANCER; MACROPHAGES; MICROPARTICLES; COMMUNICATION; MELANOMA; BIOLOGYMultiple languages
Biochemistry & Molecular Biology; Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15821

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