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Tytuł pozycji:

Simulating the human colorectal cancer microenvironment in 3D tumor-stroma co-cultures in vitro and in vivo.

Tytuł:
Simulating the human colorectal cancer microenvironment in 3D tumor-stroma co-cultures in vitro and in vivo.
Autorzy:
Devarasetty M; Wake Forest Baptist Medical Center, Winston-Salem, NC, 27101, USA.
Dominijanni A; Wake Forest Baptist Medical Center, Winston-Salem, NC, 27101, USA.
Herberg S; SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
Shelkey E; Wake Forest Baptist Medical Center, Winston-Salem, NC, 27101, USA.
Skardal A; The Ohio State University, Columbus, OH, 43210, USA.
Soker S; Wake Forest Baptist Medical Center, Winston-Salem, NC, 27101, USA. .
Źródło:
Scientific reports [Sci Rep] 2020 Jun 17; Vol. 10 (1), pp. 9832. Date of Electronic Publication: 2020 Jun 17.
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:
Coculture Techniques*
Tumor Microenvironment*
Colorectal Neoplasms/*pathology
Stromal Cells/*pathology
Biopsy ; Cell Differentiation ; Cell Line, Tumor ; Extracellular Matrix/metabolism ; Humans ; Phenotype
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Grant Information:
R33 CA202822 United States CA NCI NIH HHS; P30 CA012197 United States CA NCI NIH HHS
Entry Date(s):
Date Created: 20200620 Date Completed: 20201210 Latest Revision: 20210617
Update Code:
20240105
PubMed Central ID:
PMC7300090
DOI:
10.1038/s41598-020-66785-1
PMID:
32555362
Czasopismo naukowe
The tumor microenvironment (TME) plays a significant role in cancer progression and thus modeling it will advance our understanding of cancer growth dynamics and response to therapies. Most in vitro models are not exposed to intact body physiology, and at the same time, fail to recapitulate the extensive features of the tumor stroma. Conversely, animal models do not accurately capture the human tumor architecture. We address these deficiencies with biofabricated colorectal cancer (CRC) tissue equivalents, which are built to replicate architectural features of biopsied CRC tissue. Our data shows that tumor-stroma co-cultures consisting of aligned extracellular matrix (ECM) fibers and ordered micro-architecture induced an epithelial phenotype in CRC cells while disordered ECM drove a mesenchymal phenotype, similar to well and poorly differentiated tumors, respectively. Importantly, co-cultures studied in vitro, and upon implantation in mice, revealed similar tumor growth dynamics and retention of architectural features for 28 days. Altogether, these results are the first demonstration of replicating human tumor ECM architecture in ex vivo and in vivo cultures.
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