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2015 ; 7
(6
): 770-87
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Vasculotide reduces endothelial permeability and tumor cell extravasation in the
absence of binding to or agonistic activation of Tie2
#MMPMID25851538
Wu FT
; Lee CR
; Bogdanovic E
; Prodeus A
; Gariépy J
; Kerbel RS
EMBO Mol Med
2015[Jun]; 7
(6
): 770-87
PMID25851538
show ga
Angiopoietin-1 (Ang1) activation of Tie2 receptors on endothelial cells (ECs)
reduces adhesion by tumor cells (TCs) and limits junctional permeability to TC
diapedesis. We hypothesized that systemic therapy with Vasculotide (VT)-a
purported Ang1 mimetic, Tie2 agonist-can reduce the extravasation of potentially
metastatic circulating TCs by similarly stabilizing the host vasculature. In
vitro, VT and Ang1 treatments impeded endothelial hypermeability and the
transendothelial migration of MDA-MB-231?LM2-4 (breast), HT29 (colon), or SN12
(renal) cancer cells to varying degrees. In mice, VT treatment inhibited the
transit of TCs through the pulmonary endothelium, but not the hepatic or
lymphatic endothelium. In the in vivo LM2-4 model, VT monotherapy had no effect
on primary tumors, but significantly delayed distant metastatic dissemination to
the lungs. In the post-surgical adjuvant treatment setting, VT therapeutically
complemented sunitinib therapy, an anti-angiogenic tyrosine kinase inhibitor
which limited the local growth of residual disease. Unexpectedly, detailed
investigations into the putative mechanism of action of VT revealed no evidence
of Tie2 agonism or Tie2 binding; alternative mechanisms have yet to be
determined.