ArticleConvergent science physical oncology2017
Matrix Stiffness Enhances VEGFR-2 Internalization, Signaling, and Proliferation in Endothelial Cells.
Article in Convergent science physical oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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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.
The trial behind it
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
53 citing papers in PubMed, 79 citations in OpenAlex.
- Targeting stiffness-dependent YAP/TAZ restores angiogenesis dynamics impaired by ALK1 knockout in silico.PLoS computational biology · 2026Article
- Tumor-like proliferation of CCM3 knockout endothelial cells: insights from semaxinib treatment and transcriptome profiling of co-cultures.Acta neuropathologica communications · 2026Article
- Strain Promotes Triple Negative Breast Cancer Proliferation and Migration Via VEGFR-2.Cellular and molecular bioengineering · 2025Article
- Mechanosensing of Shear Stress and Uterine Spiral Artery Remodeling by Invasive Trophoblasts in Early Pregnancy.International journal of molecular sciences · 2025Review
- Design, synthesis, andRSC advances · 2025Article
- Angiogenesis: Biological Mechanisms and In Vitro Models.Annals of biomedical engineering · 2025Review
- Review
- Same same but different? How blood and lymphatic vessels induce cell contact inhibition.Biochemical Society transactions · 2025Review
- Effect of Mechanical Environment Alterations in 3D Stem Cell Culture on the Therapeutic Potential of Extracellular Vesicles.Biomaterials research · 2025Article
- Microvascular endothelial cells display organ-specific responses to extracellular matrix stiffness.Current research in physiology · 2025Article
- Towards propagation of epidermal cells for wound repair: glass, as cell culture substrate, enhances proliferation and migration of human keratinocytes.Frontiers in bioengineering and biotechnology · 2025Article
- Angiogenesis is limited by LIC1-mediated lysosomal trafficking.Angiogenesis · 2024Article
- Mesenchymal Osr1+ cells regulate embryonic lymphatic vessel formation.Development (Cambridge, England) · 2024Article
- The role of extracellular matrix in angiogenesis: Beyond adhesion and structure.Biomaterials and biosystems · 2024Review
- Mechanosensory entities and functionality of endothelial cells.Frontiers in cell and developmental biology · 2024Review
- Biomechanical stimulation promotes blood vessel growth despite VEGFR-2 inhibition.BMC biology · 2023Article
- Studying sprouting angiogenesis under combination of oxygen gradients and co-culture of fibroblasts using microfluidic cell culture model.Materials today. Bio · 2023Article
- Variations in mechanical stiffness alter microvascular sprouting and stability in a PEG hydrogel model of idiopathic pulmonary fibrosis.Microcirculation (New York, N.Y. : 1994) · 2023Article
- Mechanical regulation of the early stages of angiogenesis.Journal of the Royal Society, Interface · 2022Review
- Targeting the tumor stroma for cancer therapy.Molecular cancer · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Vascular endothelial growth factor (VEGF) can mediate endothelial cell migration, proliferation, and angiogenesis. During cancer progression, VEGF production is often increased to stimulate the growth of new blood vessels to supply growing tumors with the additional oxygen and nutrients they require. Extracellular matrix stiffening also occurs during tumor progression, however, the crosstalk between tumor mechanics and VEGF signaling remains poorly understood. Here, we show that matrix stiffness heightens downstream endothelial cell response to VEGF by altering VEGF receptor-2 (VEGFR-2) internalization, and this effect is influenced by cell confluency. In sub-confluent endothelial monolayers, VEGFR-2 levels, but not VEGFR-2 phosphorylation, are influenced by matrix rigidity. Interestingly, more compliant matrices correlated with increased expression and clustering of VEGFR-2; however, stiffer matrices induced increased VEGFR-2 internalization. These effects are most likely due to actin-mediated contractility, as inhibiting ROCK on stiff substrates increased VEGFR-2 clustering and decreased internalization. Additionally, increasing matrix stiffness elevates ERK 1/2 phosphorylation, resulting in increased cell proliferation. Moreover, cells on stiff matrices generate more actin stress fibers than on compliant substrates, and the addition of VEGF stimulates an increase in fiber formation regardless of stiffness. In contrast, once endothelial cells reached confluency, stiffness-enhanced VEGF signaling was no longer observed. Together, these data show a complex effect of VEGF and matrix mechanics on VEGF-induced signaling, receptor dynamics, and cell proliferation that is mediated by cell confluency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.