Journal Article

DKFZ-2018-00179

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Endothelial Tie1-mediated angiogenesis and vascular abnormalization promote tumor progression and metastasis.

La Porta, S. (First author)DKFZ* ; Roth, L.DKFZ* ; Singhal, M.DKFZ* ; Mogler, C.DKFZ* ; Spegg, C.DKFZ* ; Schieb, B.DKFZ* ; Qu, X. ; Adams, R. H. ; Baldwin, H. S. ; Savant, S. ; Augustin, H. (Last author)DKFZ*

2018
ASCJ Ann Arbor, Mich.

This record in other databases:  

Please use a persistent id in citations: doi:10.1172/JCI94674

Abstract: The endothelial tyrosine kinase receptor Tie1 remains poorly characterized, largely owing to its orphan receptor status. Global Tie1 inactivation causes late embryonic lethality, thereby reflecting its importance during development. Tie1 also plays pivotal roles during pathologies such as atherosclerosis and tumorigenesis. In order to study the contribution of Tie1 to tumor progression and metastasis, we conditionally deleted Tie1 in endothelial cells at different stages of tumor growth and metastatic dissemination. Tie1 deletion during primary tumor growth in mice led to a decrease in microvessel density and an increase in mural cell coverage with improved vessel perfusion. Reduced angiogenesis and enhanced vascular normalization resulted in a progressive increase of intratumoral necrosis that caused a growth delay only at later stages of tumor progression. Concomitantly, surgical removal of the primary tumor decreased the number of circulating tumor cells, reduced metastasis, and prolonged overall survival. Additionally, Tie1 deletion in experimental murine metastasis models prevented extravasation of tumor cells into the lungs and reduced metastatic foci. Taken together, the data support Tie1 as a therapeutic target by defining its regulatory functions during angiogenesis and vascular abnormalization and identifying its role during metastasis.

Note: DKFZ-ZMBH-Allianz

---

Contributing Institute(s):

1. A190 Vaskuläre Onkologie und Metastasierung (A190)
2. DKTK Heidelberg (L101)

Research Program(s):

1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2018

---

Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---