ArticlePloS one2015
Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed.
- The glymphatic system and glioblastoma.Brain : a journal of neurology · 2026Review
- Bioengineering facets of the tumor microenvironment in 3D tumor models: insights into cellular, biophysical and biochemical interactions.FEBS open bio · 2025Review
- The mechanopathology of the tumor microenvironment: detection techniques, molecular mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2025Review
- The influence of biophysical niche on tumor-associated macrophages in liver cancer.Hepatology communications · 2024Review
- Toward innovative approaches for exploring the mechanically regulated tumor-immune microenvironment.APL bioengineering · 2024Review
- Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine.Oncogene · 2023Review
- Fluid flow to mimic organ function in 3DAPL bioengineering · 2023Review
- The Influence of Fluid Shear Stress on Bone and Cancer Cells Proliferation and Distribution.Annals of biomedical engineering · 2023Article
- Interstitial fluid flow contributes to prostate cancer invasion and migration to bone; study conducted using a novel horizontal flow bioreactor.Biofabrication · 2023Article
- Fluids and flows in brain cancer and neurological disorders.WIREs mechanisms of disease · 2023Review
- Precision of region of interest-based tri-exponential intravoxel incoherent motion quantification and the role of the Intervoxel spatial distribution of flow velocities.Magnetic resonance in medicine · 2022Article
- Article
- Chemokine/GPCR Signaling-Mediated EMT in Cancer Metastasis.Journal of oncology · 2022Review
- CXCL2/10/12/14 are prognostic biomarkers and correlated with immune infiltration in hepatocellular carcinoma.Bioscience reports · 2021Article
- Article
- TNF-α augments CXCL10/CXCR3 axis activity to induce Epithelial-Mesenchymal Transition in colon cancer cell.International journal of biological sciences · 2021Article
- Effects of biomechanical forces on the biological behavior of cancer stem cells.Journal of Cancer · 2021Review
- Inhibition of RFX6 Suppresses the Invasive Ability of Tumor Cells Through the Notch Pathway and Affects Tumor Immunity in Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Tumor spheroids under perfusion within a 3D microfluidic platform reveal critical roles of cell-cell adhesion in tumor invasion.Scientific reports · 2020Article
- SOX4 activates CXCL12 in hepatocellular carcinoma cells to modulate endothelial cell migration and angiogenesis in vivo.Oncogene · 2020Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is the most common form of liver cancer (~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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