Title | Interstitial fluid pressure regulates collective invasion in engineered human breast tumors via Snail, vimentin, and E-cadherin. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Piotrowski-Daspit, AS, Tien, J, Nelson, CM |
Journal | Integr Biol (Camb) |
Volume | 8 |
Issue | 3 |
Pagination | 319-31 |
Date Published | 2016 Mar 14 |
ISSN | 1757-9708 |
Keywords | Breast Neoplasms, Cadherins, Cell Aggregation, Cell Engineering, Cell Line, Tumor, Cell Movement, Coculture Techniques, Epithelial-Mesenchymal Transition, Extracellular Fluid, Female, Humans, Neoplasm Invasiveness, RNA, Small Interfering, Snail Family Transcription Factors, Spheroids, Cellular, Vimentin |
Abstract | <p>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.</p> |
DOI | 10.1039/c5ib00282f |
Alternate Journal | Integr Biol (Camb) |
PubMed ID | 26853861 |
PubMed Central ID | PMC4792648 |
Grant List | R21 HL110335 / HL / NHLBI NIH HHS / United States R01 CA187692 / CA / NCI NIH HHS / United States HL110335 / HL / NHLBI NIH HHS / United States R21 HL118532 / HL / NHLBI NIH HHS / United States U54 CA143803 / CA / NCI NIH HHS / United States R01 GM083997 / GM / NIGMS NIH HHS / United States R01 HL120142 / HL / NHLBI NIH HHS / United States HL118532 / HL / NHLBI NIH HHS / United States U54CA143803 / CA / NCI NIH HHS / United States GM083997 / GM / NIGMS NIH HHS / United States CA187692 / CA / NCI NIH HHS / United States HL120142 / HL / NHLBI NIH HHS / United States |