TY - JOUR
T1 - CD36-triggered cell invasion and persistent tissue colonization by tumor microvesicles during metastasis
AU - Pfeiler, Susanne
AU - Thakur, Manovriti
AU - Gruenauer, Petra
AU - Megens, Remco T. A.
AU - Joshi, Urjita
AU - Coletti, Raffaele
AU - Samara, Verena
AU - Mueller-Stoy, Geraldine
AU - Ishikawa-Ankerhold, Hellen
AU - Stark, Konstantin
AU - Klingl, Andreas
AU - Froehlich, Thomas
AU - Arnold, Georg J.
AU - Woermann, Sonja
AU - Bruns, Christiane J.
AU - Alguel, Hana
AU - Weber, Christian
AU - Massberg, Steffen
AU - Engelmann, Bernd
N1 - Funding Information:
The authors thank Katja Reges (Institut für Laborator-iumsmedizin, Klinikum der Universität München) for preparation of CFP-TF construct, and Kathrin Gärtner (Helmholtz Zentrum München) for help with nanoparticle tracking analysis. The work was supported by SFB1123 from Deutsche Forschungsgemeinschaft (Projects B06 to S.M. and B.E., A01 to C.W., and Z01 to R.T.A.M.; INST 409/150-1 FUGG to C.W., S.M., and R.T.A.M.), by SFB1321 (Project P10 to B.E. and S.M.), as well as by grants from Deutsche Krebshilfe and Wilhelm-Sander-Stiftung (to B.E.) and SFB 914 (Project Z01 to R.C., H.I.-A., and S.M.). S.P. and M.T. shared first authorship. The authors declare no conflicts of interest.
Funding Information:
The authors thank Katja Reges (Institut f?r Laboratoriumsmedizin, Klinikum der Universit?t M?nchen) for preparation of CFP-TF construct, and Kathrin G?rtner (Helmholtz Zentrum M?nchen) for help with nanoparticle tracking analysis. The work was supported by SFB1123 from Deutsche Forschungsgemeinschaft (Projects B06 to S.M. and B.E., A01 to C.W., and Z01 to R.T.A.M.; INST 409/150-1 FUGG to C.W., S.M., and R.T.A.M.), by SFB1321 (Project P10 to B.E. and S.M.), as well as by grants from Deutsche Krebshilfe and Wilhelm-Sander-Stiftung (to B.E.) and SFB 914 (Project Z01 to R.C., H.I.-A., and S.M.). S.P. and M.T. shared first authorship. The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - super-resolution microscopy
KW - microvesicle extravasation
KW - Ly6C(-)macrophages
KW - EXTRACELLULAR VESICLES
KW - CANCER
KW - MACROPHAGES
KW - MICROPARTICLES
KW - COMMUNICATION
KW - MELANOMA
KW - BIOLOGY
U2 - 10.1096/fj.201800985R
DO - 10.1096/fj.201800985R
M3 - Article
C2 - 30207797
SN - 0892-6638
VL - 33
SP - 1860
EP - 1872
JO - Faseb Journal
JF - Faseb Journal
IS - 2
ER -