title: Amphiphilic suramin dissolves Matrigel, causing an 'inhibition' artefact within in vitro angiogenesis assays.
abstract: The field of study concerning promotion and/or inhibition of angiogenesis has gathered much attention in the scientific community. A great deal of work has been invested towards defining reproducible assays to gauge for promotion or inhibition of angiogenesis in response to drug treatments or growth conditions. Two common components of these assays were noted by our group to have an unexpected and previously unreported interaction. Suramin is a commercially available compound, commonly used as a positive control for in vitro angiogenic inhibition assays. Matrigel is a popular extracellular substrate that supports angiogenic network formation when endothelial cells are cultured on its surface. However, our group demonstrated that suramin alone (without the presence of cells) will actively dissolve Matrigel, causing the extracellular matrix to transition from the gel-like physical state to a more liquid state. This causes cells on the Matrigel to congregate and sink to the bottom of the well. Therefore, previous observations of inhibition of endothelial cell angiogenesis through the incubation with suramin (including previous observations made by our group) are, largely, an artefact caused by suramin and matrix interaction rather than suramin and cells interaction, as previously reported. Our results suggest that the presence of sulphate groups and amphiphilic properties of suramin are likely responsible for the disruption of the matrix layer. We believe that this information is of prime importance to anyone using similar in vitro models, or employing suramin in any therapy or drug development assays.
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, CA, USA; Vala Sciences Inc., San Diego, CA, USA.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Prigozhina
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Heisel
authors.forename: Jordan R
authors.initials: JR
authors.lastname: Seldeen
authors.forename: Nicholas D P
authors.initials: ND
authors.lastname: Cosford
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Price
mesh_terms: D016477:Artifacts; D001681:Biological Assay / Q000379:methods*; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects*; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011509:Proteoglycans / Q000187:drug effects*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013498:Suramin / Q000737:chemistry / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D007797:Laminin; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D013501:Surface-Active Agents; C029967:nidogen; C059485:matrigel; D012967:Sodium Dodecyl Sulfate; D013498:Suramin; D003094:Collagen
keywords: Matrigel; endothelial; extracellular matrix; in vitro angiogenesis assay; suramin