A 3D tumor microenvironment regulates cell proliferation, peritoneal growth and expression patterns
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A 3D tumor microenvironment regulates cell proliferation, peritoneal growth and expression patterns. / Loessner, Daniela; Rockstroh, Anja; Shokoohmand, Ali; Holzapfel, Boris M; Wagner, Ferdinand; Baldwin, Jeremy; Boxberg, Melanie; Schmalfeldt, Barbara; Lengyel, Ernst; Clements, Judith A; Hutmacher, Dietmar W.
In: BIOMATERIALS, Vol. 190-191, 01.2019, p. 63-75.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A 3D tumor microenvironment regulates cell proliferation, peritoneal growth and expression patterns
AU - Loessner, Daniela
AU - Rockstroh, Anja
AU - Shokoohmand, Ali
AU - Holzapfel, Boris M
AU - Wagner, Ferdinand
AU - Baldwin, Jeremy
AU - Boxberg, Melanie
AU - Schmalfeldt, Barbara
AU - Lengyel, Ernst
AU - Clements, Judith A
AU - Hutmacher, Dietmar W
N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.
PY - 2019/1
Y1 - 2019/1
N2 - Peritoneal invasion through the mesothelial cell layer is a hallmark of ovarian cancer metastasis. Using tissue engineering technologies, we recreated an ovarian tumor microenvironment replicating this aspect of disease progression. Ovarian cancer cell-laden hydrogels were combined with mesothelial cell-layered melt electrospun written scaffolds and characterized with proliferation and transcriptomic analyses and used as intraperitoneal xenografts. Here we show increased cancer cell proliferation in these 3D co-cultures, which we validated using patient-derived cells and linked to peritoneal tumor growth in vivo. Transcriptome-wide expression analysis identified IGFBP7, PTGS2, VEGFC and FGF2 as bidirectional factors deregulated in 3D co-cultures compared to 3D mono-cultures, which we confirmed by immunohistochemistry of xenograft and patient-derived tumor tissues and correlated with overall and progression-free survival. These factors were further increased upon expression of kallikrein-related proteases. This clinically predictive model allows us to mimic the complexity and processes of the metastatic disease that may lead to therapies that protect from peritoneal invasion or delay the development of metastasis.
AB - Peritoneal invasion through the mesothelial cell layer is a hallmark of ovarian cancer metastasis. Using tissue engineering technologies, we recreated an ovarian tumor microenvironment replicating this aspect of disease progression. Ovarian cancer cell-laden hydrogels were combined with mesothelial cell-layered melt electrospun written scaffolds and characterized with proliferation and transcriptomic analyses and used as intraperitoneal xenografts. Here we show increased cancer cell proliferation in these 3D co-cultures, which we validated using patient-derived cells and linked to peritoneal tumor growth in vivo. Transcriptome-wide expression analysis identified IGFBP7, PTGS2, VEGFC and FGF2 as bidirectional factors deregulated in 3D co-cultures compared to 3D mono-cultures, which we confirmed by immunohistochemistry of xenograft and patient-derived tumor tissues and correlated with overall and progression-free survival. These factors were further increased upon expression of kallikrein-related proteases. This clinically predictive model allows us to mimic the complexity and processes of the metastatic disease that may lead to therapies that protect from peritoneal invasion or delay the development of metastasis.
KW - Journal Article
U2 - 10.1016/j.biomaterials.2018.10.014
DO - 10.1016/j.biomaterials.2018.10.014
M3 - SCORING: Journal article
C2 - 30396040
VL - 190-191
SP - 63
EP - 75
JO - BIOMATERIALS
JF - BIOMATERIALS
SN - 0142-9612
ER -
