TY  - JOUR
A1  - Justin, Saira
A1  - Rutz, Jochen
A1  - Maxeiner, Sebastian
A1  - Chun, Felix
A1  - Jüngel, Eva
A1  - Blaheta, Roman A.
T1  - Bladder cancer metastasis induced by chronic everolimus application can be counteracted by sulforaphane in vitro
T2  - International journal of molecular sciences
N2  - Chronic treatment with the mTOR inhibitor, everolimus, fails long-term in preventing tumor growth and dissemination in cancer patients. Thus, patients experiencing treatment resistance seek complementary measures, hoping to improve therapeutic efficacy. This study investigated metastatic characteristics of bladder carcinoma cells exposed to everolimus combined with the isothiocyanate sulforaphane (SFN), which has been shown to exert cancer inhibiting properties. RT112, UMUC3, or TCCSUP bladder carcinoma cells were exposed short- (24 h) or long-term (8 weeks) to everolimus (0.5 nM) or SFN (2.5 µM), alone or in combination. Adhesion and chemotaxis along with profiling details of CD44 receptor variants (v) and integrin α and β subtypes were evaluated. The functional impact of CD44 and integrins was explored by blocking studies and siRNA knock-down. Long-term exposure to everolimus enhanced chemotactic activity, whereas long-term exposure to SFN or the SFN-everolimus combination diminished chemotaxis. CD44v4 and v7 increased on RT112 cells following exposure to SFN or SFN-everolimus. Up-regulation of the integrins α6, αV, and β1 and down-regulation of β4 that was present with everolimus alone could be prevented by combining SFN and everolimus. Down-regulation of αV, β1, and β4 reduced chemotactic activity, whereas knock-down of CD44 correlated with enhanced chemotaxis. SFN could, therefore, inhibit resistance-related tumor dissemination during everolimus-based bladder cancer treatment.
KW  - sulforaphane
KW  - bladder cancer
KW  - adhesion
KW  - chemotaxis
KW  - integrins
KW  - CD44
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/55492
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-554925
SN  - 1422-0067
N1  - © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
VL  - 21
IS  - 15, art. 5582
SP  - 1
EP  - 14
PB  - MDPI
CY  - Basel
ER  -