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@ARTICLE{Pervaiz:142993,
author = {A. Pervaiz$^*$ and M. Zepp$^*$ and S. Mahmood and D. M.
Ali$^*$ and M. Berger$^*$ and H. Adwan$^*$},
title = {{CCR}5 blockage by maraviroc: a potential therapeutic
option for metastatic breast cancer.},
journal = {Cellular oncology},
volume = {42},
number = {1},
issn = {2211-3436},
address = {Heidelberg [u.a.]},
publisher = {Springer},
reportid = {DKFZ-2019-00618},
pages = {93 - 106},
year = {2019},
abstract = {Bone metastasis is observed in up to $70\%$ of breast
cancer patients. The currently available treatment options
are palliative in nature. Chemokine receptor 5 (CCR5) has
gained attention as therapeutic target in various
malignancies. Here, we investigated the effects of targeting
CCR5 by its antagonist maraviroc in metastatic breast cancer
cells.In response to maraviroc exposure, cytotoxicity was
assessed using an MTT proliferation assay, whereas the
effects on colony formation and migration were assessed
using colony formation, transwell chamber migration and
scratch wound healing assays, respectively.
Apoptosis-related activities were investigated using nuclear
staining, annexin-V FITC staining and Western blotting. Cell
cycle changes were analysed using flow cytometry and qRT-PCR
for cell cycle relevant genes. A nude rat model for breast
cancer bone metastasis was used to evaluate the in vivo
efficacy of CCR5 targeting by maraviroc. Circulatory levels
of the three cognate ligands for CCR5 (CCL3, CCL4, CCL5)
were analysed in sera of breast cancer patients using
ELISA.We found that blockade of CCR5 attenuated the
proliferation, colony formation and migration of metastatic
breast cancer cells, and induced apoptosis and arrest in the
G1 phase of the cell cycle. Expression profiling highlighted
the involvement of cell cycle related signalling cascades.
We also found that treatment with maraviroc significantly
inhibited bone metastasis in nude rats implanted with
MDA-MB-231 breast cancer cells. Finally, we found that the
circulatory levels of three cognate ligands for the CCR5
receptor varied between breast cancer patients and healthy
controls.Our findings indicate that targeting CCR5 may be an
effective strategy to combat breast cancer bone metastasis.},
cin = {G401},
ddc = {610},
cid = {I:(DE-He78)G401-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30456574},
doi = {10.1007/s13402-018-0415-3},
url = {https://inrepo02.dkfz.de/record/142993},
}