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@ARTICLE{Li:182780,
author = {A. Li and S. Muenst and J. Hoffman and L. Starck and M.
Sarem and A. Fischer$^*$ and G. Hutter and V. P. Shastri},
title = {{M}esenchymal-endothelial nexus in breast cancer spheroids
induces vasculogenesis and local invasion in a {CAM} model.},
journal = {Communications biology},
volume = {5},
number = {1},
issn = {2399-3642},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2022-02912},
pages = {1303},
year = {2022},
abstract = {Interplay between non-cancerous cells (immune, fibroblasts,
mesenchymal stromal cells (MSC), and endothelial cells (EC))
has been identified as vital in driving tumor progression.
As studying such interactions in vivo is challenging, ex
vivo systems that can recapitulate in vivo scenarios can aid
in unraveling the factors impacting tumorigenesis and
metastasis. Using the synthetic tumor microenvironment
mimics (STEMs)-a spheroid system composed of breast cancer
cells (BCC) with defined human MSC and EC fractions, here we
show that EC organization into vascular structures is BC
phenotype dependent, and independent of ERα expression in
epithelial cancer cells, and involves MSC-mediated Notch1
signaling. In a 3D-bioprinted model system to mimic local
invasion, MDA STEMs collectively respond to serum gradient
and form invading cell clusters. STEMs grown on chick
chorioallantoic membrane undergo local invasion to form CAM
tumors that can anastomose with host vasculature and bear
the typical hallmarks of human BC and this process requires
both EC and MSC. This study provides a framework for
developing well-defined in vitro systems, including
patient-derived xenografts that recapitulate in vivo events,
to investigate heterotypic cell interactions in tumors, to
identify factors promoting tumor metastasis-related events,
and possibly drug screening in the context of personalized
medicine.},
cin = {A270},
ddc = {570},
cid = {I:(DE-He78)A270-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36435836},
doi = {10.1038/s42003-022-04236-5},
url = {https://inrepo02.dkfz.de/record/182780},
}