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两亲性苏拉明溶解 Matrigel,导致体外血管生成试验中出现“抑制”假象。

Amphiphilic suramin dissolves Matrigel, causing an 'inhibition' artefact within in vitro angiogenesis assays.

机构信息

Sanford-Burnham Medical Research Institute, La Jolla, CA, USA; Vala Sciences Inc., San Diego, CA, USA.

出版信息

Int J Exp Pathol. 2013 Dec;94(6):412-7. doi: 10.1111/iep.12043. Epub 2013 Sep 2.

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.

摘要

在科学界,有关促进和/或抑制血管生成的研究领域引起了广泛关注。为了定义可重现的测定法,以衡量药物治疗或生长条件下对血管生成的促进或抑制作用,人们投入了大量的工作。我们小组注意到,这些测定法中的两个常见成分具有出乎意料的、以前未报道过的相互作用。苏拉明是一种市售的化合物,常用于体外血管生成抑制测定的阳性对照。Matrigel 是一种流行的细胞外基质,当内皮细胞在其表面培养时,它支持血管生成网络的形成。然而,我们小组证明,单独的苏拉明(没有细胞存在)会积极溶解 Matrigel,导致细胞外基质从凝胶状物理状态转变为更液态的状态。这会导致 Matrigel 上的细胞聚集并下沉到孔的底部。因此,以前通过苏拉明孵育观察到的内皮细胞血管生成抑制(包括我们小组以前的观察结果),在很大程度上是苏拉明与基质相互作用而不是苏拉明与细胞相互作用造成的假象,如前所述。我们的结果表明,苏拉明的硫酸盐基团和两亲性质可能是破坏基质层的原因。我们相信,对于任何使用类似体外模型的人,或者在任何治疗或药物开发测定中使用苏拉明的人,这些信息都是至关重要的。

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