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2017 ; 8
(44
): 77622-77633
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
The pretubulysin-induced exposure of collagen is caused by endothelial cell
retraction that results in an increased adhesion and decreased transmigration of
tumor cells
#MMPMID29100413
Schwenk R
; Stehning T
; Bischoff I
; Ullrich A
; Kazmaier U
; Fürst R
Oncotarget
2017[Sep]; 8
(44
): 77622-77633
PMID29100413
show ga
Microtubule-targeting agents (MTAs) are the most widely used chemotherapeutic
drugs. Pretubulysin (PT), a biosynthetic precursor of the myxobacterial
tubulysins, was recently identified as a novel MTA. Besides its strong
anti-tumoral activities, PT attenuates tumor angiogenesis, exerts anti-vascular
actions on tumor vessels and decreases cancer metastasis formation in vivo. The
aim of the present study was to analyze the impact of PT on the interaction of
endothelial and tumor cells in vitro to gain insights into the mechanism
underlying its anti-metastatic effect. The influence of PT on tumor cell adhesion
and transmigration onto/through the endothelium as well as its influence on cell
adhesion molecules and the chemokine system CXCL12/CXCR4 was investigated.
Treatment of human endothelial cells with PT increased the adhesion of breast
cancer cells to the endothelial monolayer, whereas their transmigration through
the endothelium was strongly reduced. Interestingly, the PT-induced upregulation
of ICAM-1, VCAM-1 and CXCL12 were dispensable for the PT-evoked tumor cell
adhesion. Tumor cells preferred to adhere to collagen exposed within PT-triggered
endothelial gaps via ?1-integrins on the tumor cell surface. Taken together, our
study provides, at least in part, an explanation for the anti-metastatic
potential of PT.