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一种新的细胞负载的 3D 藻酸盐-基质胶水凝胶类似于在体观察到的人乳腺癌细胞的恶性形态、扩散和侵袭能力。

A new cell-laden 3D Alginate-Matrigel hydrogel resembles human breast cancer cell malignant morphology, spread and invasion capability observed "in vivo".

机构信息

National Research Council (CNR) - IEIIT Institute, Genoa, 16149, Italy.

Department of Biophysical and Electronic Engineering (DIBRIS), University of Genoa, Genoa, 16145, Italy.

出版信息

Sci Rep. 2018 Mar 28;8(1):5333. doi: 10.1038/s41598-018-23250-4.

Abstract

Purpose of this study was the development of a 3D material to be used as substrate for breast cancer cell culture. We developed composite gels constituted by different concentrations of Alginate (A) and Matrigel (M) to obtain a structurally stable-in-time and biologically active substrate. Human aggressive breast cancer cells (i.e. MDA-MB-231) were cultured within the gels. Known the link between cell morphology and malignancy, cells were morphologically characterized and their invasiveness correlated through an innovative bioreactor-based invasion assay. A particular type of gel (i.e. 50% Alginate, 50% Matrigel) emerged thanks to a series of significant results: 1. cells exhibited peculiar cytoskeleton shapes and nuclear fragmentation characteristic of their malignancy; 2. cells expressed the formation of the so-called invadopodia, actin-based protrusion of the plasma membrane through which cells anchor to the extracellular matrix; 3. cells were able to migrate through the gels and attach to an engineered membrane mimicking the vascular walls hosted within bioreactor, providing a completely new 3D in vitro model of the very precursor steps of metastasis.

摘要

本研究旨在开发一种可作为乳腺癌细胞培养基底的 3D 材料。我们开发了由不同浓度藻酸盐(A)和基质胶(M)组成的复合凝胶,以获得结构稳定且具有生物活性的基底。人乳腺癌侵袭细胞(即 MDA-MB-231)在凝胶内培养。众所周知,细胞形态与恶性之间存在关联,因此通过一种创新性的基于生物反应器的侵袭测定法对细胞进行形态学特征分析及其侵袭性进行相关性分析。由于一系列显著结果,出现了一种特殊类型的凝胶(即 50%藻酸盐,50%基质胶):1. 细胞表现出具有其恶性特征的独特细胞骨架形状和核碎片化;2. 细胞表达了所谓的侵袭伪足的形成,即通过细胞膜的肌动蛋白基突起,细胞通过该突起附着在细胞外基质上;3. 细胞能够穿过凝胶并附着在生物反应器内模拟血管壁的工程化膜上,为转移的非常早期步骤提供了一个全新的 3D 体外模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c01b/5871779/f0dcdc854a28/41598_2018_23250_Fig1_HTML.jpg

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