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Identification of Extracellular Matrix Proteins Secreted by Human Dermal Fibroblasts Cultured in 3D Electrospun Scaffolds

Malakpour Permlid, Atena LU ; Buzzi, Irina ; Hegardt, Cecilia LU ; Johansson, Fredrik LU and Oredsson, Stina LU (2021) In Scientific Reports 11.
Abstract
The appreciation that cell interactions in tissues is dependent on their three dimensional (3D) distribution has stimulated the development of 3D cell culture models. We constructed an artificial 3D tumour by culturing human breast cancer JIMT-1 cells and human dermal fibroblasts (HDFs) in a 3D network of electrospun polycaprolactone fibres. Here, we investigate ECM components produced by the cells in the artificial 3D tumour, which is an important step in validating the model. Immunostaining and confocal fluorescence microscopy show that the ECM proteins fibronectin, collagen I, and laminin are deposited throughout the entire 3D structure. Secreted soluble factors including matrix metalloproteinases (MMPs) and interleukine-6 (IL-6) were... (More)
The appreciation that cell interactions in tissues is dependent on their three dimensional (3D) distribution has stimulated the development of 3D cell culture models. We constructed an artificial 3D tumour by culturing human breast cancer JIMT-1 cells and human dermal fibroblasts (HDFs) in a 3D network of electrospun polycaprolactone fibres. Here, we investigate ECM components produced by the cells in the artificial 3D tumour, which is an important step in validating the model. Immunostaining and confocal fluorescence microscopy show that the ECM proteins fibronectin, collagen I, and laminin are deposited throughout the entire 3D structure. Secreted soluble factors including matrix metalloproteinases (MMPs) and interleukine-6 (IL-6) were analysed in collected medium and were found to be mainly derived from the HDFs. Treatment with transforming growth factor-β1 (TGF-β1), a major cytokine found in a tumour, significantly alters the MMP activity and IL-6 concentration. In addition, TGF-β1 treatment, changes the morphology of the HDFs to become more elongated and with increased linearized actin filaments compared to non-treated HDFs. Collectively, these novel findings suggest that the artificial 3D tumour displays a clear cell distribution and ECM deposition that resembles a tumour environment in vivo, suggesting an innovative biological model to study a human tumour. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
11
article number
6655
pages
18 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85103206944
  • pmid:33758206
ISSN
2045-2322
DOI
10.1038/s41598-021-85742-0
language
English
LU publication?
yes
id
a4a1d6d6-2c21-43d4-be04-38d3a538fdea
date added to LUP
2021-03-01 21:19:21
date last changed
2023-11-20 23:45:52
@article{a4a1d6d6-2c21-43d4-be04-38d3a538fdea,
  abstract     = {{The appreciation that cell interactions in tissues is dependent on their three dimensional (3D) distribution has stimulated the development of 3D cell culture models. We constructed an artificial 3D tumour by culturing human breast cancer JIMT-1 cells and human dermal fibroblasts (HDFs) in a 3D network of electrospun polycaprolactone fibres. Here, we investigate ECM components produced by the cells in the artificial 3D tumour, which is an important step in validating the model. Immunostaining and confocal fluorescence microscopy show that the ECM proteins fibronectin, collagen I, and laminin are deposited throughout the entire 3D structure. Secreted soluble factors including matrix metalloproteinases (MMPs) and interleukine-6 (IL-6) were analysed in collected medium and were found to be mainly derived from the HDFs. Treatment with transforming growth factor-β1 (TGF-β1), a major cytokine found in a tumour, significantly alters the MMP activity and IL-6 concentration. In addition, TGF-β1 treatment, changes the morphology of the HDFs to become more elongated and with increased linearized actin filaments compared to non-treated HDFs. Collectively, these novel findings suggest that the artificial 3D tumour displays a clear cell distribution and ECM deposition that resembles a tumour environment in vivo, suggesting an innovative biological model to study a human tumour.}},
  author       = {{Malakpour Permlid, Atena and Buzzi, Irina and Hegardt, Cecilia and Johansson, Fredrik and Oredsson, Stina}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Identification of Extracellular Matrix Proteins Secreted by Human Dermal Fibroblasts Cultured in 3D Electrospun Scaffolds}},
  url          = {{http://dx.doi.org/10.1038/s41598-021-85742-0}},
  doi          = {{10.1038/s41598-021-85742-0}},
  volume       = {{11}},
  year         = {{2021}},
}