TY - JOUR
T1 - Interstitial fluid pressure regulates collective invasion in engineered human breast tumors via Snail, vimentin, and E-cadherin
AU - Piotrowski-Daspit, Alexandra S.
AU - Tien, Joe
AU - Nelson, Celeste M.
N1 - Funding Information:
We thank Virginia Lane for her assistance in preparing samples and members of the Tissue Morphodynamics Group for their insightful comments. This work was supported in part by grants from the NIH (GM083997, HL110335, HL118532, HL120142, and CA187692), pilot project funding from the NIH/NCI Physical Sciences-Oncology Center at Princeton University (U54CA143803), Concept Award W81XWH-09-1-0565 from the Breast Cancer Research Program of the Department of Defense (to J. T.), the David & Lucile Packard Foundation, the Alfred P. Sloan Foundation, and the Camille & Henry Dreyfus Foundation. C. M. N. holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. A. S. P. was supported in part by a Charlotte Elizabeth Procter Honorific Fellowship.
Publisher Copyright:
© 2016 The Royal Society of Chemistry.
PY - 2016/3
Y1 - 2016/3
N2 - Many solid tumors exhibit elevated interstitial fluid pressure (IFP). This elevated pressure within the core of the tumor results in outward flow of interstitial fluid to the tumor periphery. We previously found that the directionality of IFP gradients modulates collective invasion from the surface of patterned three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. Here, we used this 3D engineered tumor model to investigate the molecular mechanisms underlying IFP-induced changes in invasive phenotype. We found that IFP alters the expression of genes associated with epithelial-mesenchymal transition (EMT). Specifically, the levels of Snail, vimentin, and E-cadherin were increased under pressure conditions that promoted collective invasion. These changes in gene expression were sufficient to direct collective invasion in response to IFP. Furthermore, we found that IFP modulates the motility and persistence of individual cells within the aggregates, which are also influenced by the expression levels of EMT markers. Together, these data provide insight into the molecular mechanisms that guide collective invasion from primary tumors in response to IFP.
AB - Many solid tumors exhibit elevated interstitial fluid pressure (IFP). This elevated pressure within the core of the tumor results in outward flow of interstitial fluid to the tumor periphery. We previously found that the directionality of IFP gradients modulates collective invasion from the surface of patterned three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. Here, we used this 3D engineered tumor model to investigate the molecular mechanisms underlying IFP-induced changes in invasive phenotype. We found that IFP alters the expression of genes associated with epithelial-mesenchymal transition (EMT). Specifically, the levels of Snail, vimentin, and E-cadherin were increased under pressure conditions that promoted collective invasion. These changes in gene expression were sufficient to direct collective invasion in response to IFP. Furthermore, we found that IFP modulates the motility and persistence of individual cells within the aggregates, which are also influenced by the expression levels of EMT markers. Together, these data provide insight into the molecular mechanisms that guide collective invasion from primary tumors in response to IFP.
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U2 - 10.1039/c5ib00282f
DO - 10.1039/c5ib00282f
M3 - Article
C2 - 26853861
AN - SCOPUS:84960962968
SN - 1757-9694
VL - 8
SP - 319
EP - 331
JO - Integrative Biology (United Kingdom)
JF - Integrative Biology (United Kingdom)
IS - 3
ER -