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Journal article
Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling
PloS one, v 10(11), pp e0142337-e0142337
11 Nov 2015
PMID: 26560447
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hepatocellular carcinoma (HCC) is the most common form of liver cancer (similar to 80%), and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF) on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients.
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Details
- Title
- Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling
- Creators
- Arpit D. Shah - Drexel UniversityMichael J. Bouchard - Drexel UniversityAdrian C. Shieh - Drexel University
- Publication Details
- PloS one, v 10(11), pp e0142337-e0142337
- Publisher
- Public Library Science
- Number of pages
- 17
- Grant note
- Pennsylvania Department of Health Drexel University
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000364433100072
- Scopus ID
- 2-s2.0-84955447415
- Other Identifier
- 991019169616604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Oncology