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Wolf, M.J.* ; Hoos, A.* ; Bauer, J. ; Boettcher, S.* ; Knust, M.* ; Weber, A.* ; Simonavicius, N. ; Schneider, C.* ; Lang, M.* ; Stürzl, M.* ; Croner, R.S.* ; Konrad, A.* ; Manz, M.G.* ; Moch, H.* ; Aguzzi, A.* ; van Loo, G.* ; Pasparakis, M.* ; Prinz, M.* ; Borsig, L.* ; Heikenwälder, M.

Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway.

Cancer Cell 22, 91-105 (2012)
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Increased expression of the chemokine CCL2 in tumor cells correlates with enhanced metastasis, poor prognosis, and recruitment of CCR2(+)Ly6C(hi) monocytes. However, the mechanisms driving tumor cell extravasation through the endothelium remain elusive. Here, we describe CCL2 upregulation in metastatic UICC stage IV colon carcinomas and demonstrate that tumor cell-derived CCL2 activates the CCR2(+) endothelium to increase vascular permeability in vivo. CCR2 deficiency prevents colon carcinoma extravasation and metastasis. Of note, CCR2 expression on radio-resistant cells or endothelial CCR2 expression restores extravasation and metastasis in Ccr2(-/-) mice. Reduction of CCR2 expression on myeloid cells decreases but does not prevent metastasis. CCL2-induced vascular permeability and metastasis is dependent on JAK2-Stat5 and p38MAPK signaling. Our study identifies potential targets for treating CCL2-dependent metastasis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter CHEMOKINE RECEPTOR 2; INFLAMMATORY MONOCYTES; TUMOR-METASTASIS; MYELOID CELLS; CANCER-CELLS; L-SELECTIN; MICE; CCL2; MIGRATION; LUNG
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Zeitschrift Cancer Cell
Quellenangaben Band: 22, Heft: 1, Seiten: 91-105 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed