Mechanism of a flow-gated angiogenesis switch: early signaling events at cell–matrix and cell–cell junctions
A bias towards angiogenesis from the venous circulation has long been known, but its cause remains unclear. Here we explore the possibility that high interstitial pressure in tumors and the resultant net filtration pressure gradient that would induce flow from the interstitium into the venous circul...
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| Format: | Article |
| Language: | en_US |
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Royal Society of Chemistry
2014
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| Online Access: | http://hdl.handle.net/1721.1/89235 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1826216381022994432 |
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| author | Vickerman, Vernella Kamm, Roger Dale |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Vickerman, Vernella Kamm, Roger Dale |
| author_sort | Vickerman, Vernella |
| collection | MIT |
| description | A bias towards angiogenesis from the venous circulation has long been known, but its cause remains unclear. Here we explore the possibility that high interstitial pressure in tumors and the resultant net filtration pressure gradient that would induce flow from the interstitium into the venous circulation or lymphatics could also be an important mechanical regulator of angiogenesis. The objective of this study was to test the hypothesis that basal-to-apical (B–A) transendothelial flow promotes angiogenesis and to investigate potential mechanisms. Macro- and microvascular endothelial monolayers were cultured on type I collagen gels in a microfluidic cell culture device and subjected to apical-to-basal (A–B) and B–A transendothelial flows. Samples were perfusion fixed and analyzed for morphological responses, localization and degree of phosphorylation of certain signaling proteins. Application of B–A, but not A–B flow, to cultured endothelial monolayers was found to promote capillary morphogenesis and resulted in distinct localization patterns of VE-cadherin and increased FAK phosphorylation. These results suggest that B–A flow triggers the transition of vascular endothelial cells from a quiescent to invasive phenotype and that the flow-mediated response involves signaling at cell–cell and cell–matrix interfaces. These results support the hypothesis that transendothelial pressure gradients resulting in B–A flow promotes sprouting angiogenesis and are consistent with early observations that tumor angiogenesis occurs from the venous side of the circulation. |
| first_indexed | 2024-09-23T16:46:24Z |
| format | Article |
| id | mit-1721.1/89235 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:46:24Z |
| publishDate | 2014 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | mit-1721.1/892352022-09-29T21:24:19Z Mechanism of a flow-gated angiogenesis switch: early signaling events at cell–matrix and cell–cell junctions Vickerman, Vernella Kamm, Roger Dale Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Vickerman, Vernella Kamm, Roger Dale A bias towards angiogenesis from the venous circulation has long been known, but its cause remains unclear. Here we explore the possibility that high interstitial pressure in tumors and the resultant net filtration pressure gradient that would induce flow from the interstitium into the venous circulation or lymphatics could also be an important mechanical regulator of angiogenesis. The objective of this study was to test the hypothesis that basal-to-apical (B–A) transendothelial flow promotes angiogenesis and to investigate potential mechanisms. Macro- and microvascular endothelial monolayers were cultured on type I collagen gels in a microfluidic cell culture device and subjected to apical-to-basal (A–B) and B–A transendothelial flows. Samples were perfusion fixed and analyzed for morphological responses, localization and degree of phosphorylation of certain signaling proteins. Application of B–A, but not A–B flow, to cultured endothelial monolayers was found to promote capillary morphogenesis and resulted in distinct localization patterns of VE-cadherin and increased FAK phosphorylation. These results suggest that B–A flow triggers the transition of vascular endothelial cells from a quiescent to invasive phenotype and that the flow-mediated response involves signaling at cell–cell and cell–matrix interfaces. These results support the hypothesis that transendothelial pressure gradients resulting in B–A flow promotes sprouting angiogenesis and are consistent with early observations that tumor angiogenesis occurs from the venous side of the circulation. National Institute for Biomedical Imaging and Bioengineering (U.S.) (EB003805) National Science Foundation (U.S.) (STC CBET-0939511) National Science Foundation (U.S.). Office of Emerging Frontiers in Research and Innovation (0735997) 2014-09-09T16:26:23Z 2014-09-09T16:26:23Z 2012-05 2011-12 Article http://purl.org/eprint/type/JournalArticle 1757-9694 1757-9708 http://hdl.handle.net/1721.1/89235 Vickerman, Vernella, and Roger D. Kamm. “Mechanism of a Flow-Gated Angiogenesis Switch: Early Signaling Events at Cell–matrix and Cell–cell Junctions.” Integr. Biol. 4, no. 8 (2012): 863. https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1039/c2ib00184e Integrative Biology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Royal Society of Chemistry PMC |
| spellingShingle | Vickerman, Vernella Kamm, Roger Dale Mechanism of a flow-gated angiogenesis switch: early signaling events at cell–matrix and cell–cell junctions |
| title | Mechanism of a flow-gated angiogenesis switch: early signaling events at cell–matrix and cell–cell junctions |
| title_full | Mechanism of a flow-gated angiogenesis switch: early signaling events at cell–matrix and cell–cell junctions |
| title_fullStr | Mechanism of a flow-gated angiogenesis switch: early signaling events at cell–matrix and cell–cell junctions |
| title_full_unstemmed | Mechanism of a flow-gated angiogenesis switch: early signaling events at cell–matrix and cell–cell junctions |
| title_short | Mechanism of a flow-gated angiogenesis switch: early signaling events at cell–matrix and cell–cell junctions |
| title_sort | mechanism of a flow gated angiogenesis switch early signaling events at cell matrix and cell cell junctions |
| url | http://hdl.handle.net/1721.1/89235 https://orcid.org/0000-0002-7232-304X |
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