A cell-ECM screening method to predict breast cancer metastasis.
A cell-ECM screening method to predict breast cancer metastasis.
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DOI：
10.1039/c4ib00218k
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发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Peyton SR
中科院分区：
文献类型：
--
作者：
Barney LE;Dandley EC;Jansen LE;Reich NG;Mercurio AM;Peyton SR
乳腺癌优先扩散到骨、脑、肝和肺。这种组织特异性扩散（向性）的临床模式不能仅用血流来解释，但我们对介导这些物理和化学不同组织向性的理解是有限的。虽然微环境已被认为是一个关键因素，在管理转移定植，细胞外基质（ECM）在介导向性的作用还没有得到彻底的探讨。我们创建了一个简单的生物材料平台，系统控制ECM蛋白密度和组成，以确定整合素结合是否控制转移细胞如何在次级组织部位之间分化。我们没有检查个体行为，而是汇编了与这些受控ECM上的粘附和迁移相关的表型的大模式。通过将这种新的分析与简单的生物材料平台相结合，我们创建了一种预测体内转移的体外指纹。这种快速的生物材料筛选还提供了β1，α2和α6整合素如何介导患者转移的信息，提供了超越纯遗传分析的见解。我们提出，这种在许多不同的异质细胞系中筛选许多细胞-ECM相互作用的方法可以预测体内行为，并且比复杂的3D环境或小鼠模型更简单，更快，更经济。我们还建议，当专门应用于乳腺癌的组织嗜性问题，它可以用来提供洞察某些整合素亚基作为治疗靶点。我们开发了一种高通量的方法来快速筛选生物材料表面上的细胞粘附、运动和生长因子反应。这种方法类似于系统生物学，依靠细胞表型代替遗传学。我们使用这种技术来揭示与乳腺癌转移到可能的组织部位（骨，脑，肺）相关的表型模式。通过比较只转移到一个组织部位的细胞系与异质细胞系之间的表型模式，我们提供了第一种将体外表型与体内命运联系起来的方法。这种方法在没有遗传分析的情况下是成功的，但它也预测了与整合素基因表达相关的结果，可能识别组织特异性转移的新靶点。
Breast cancer preferentially spreads to the bone, brain, liver, and lung. The clinical patterns of this tissue-specific spread (tropism) cannot be explained by blood flow alone, yet our understanding of what mediates tropism to these physically and chemically diverse tissues is limited. While the microenvironment has been recognized as a critical factor in governing metastatic colonization, the role of the extracellular matrix (ECM) in mediating tropism has not been thoroughly explored. We created a simple biomaterial platform with systematic control over the ECM protein density and composition to determine if integrin binding governs how metastatic cells differentiate between secondary tissue sites. Instead of examining individual behaviors, we compiled large patterns of phenotypes associated with adhesion to and migration on these controlled ECMs. In combining this novel analysis with a simple biomaterial platform, we created an in vitro fingerprint that is predictive of in vivo metastasis. This rapid biomaterial screen also provided information on how β1, α2, and α6 integrins might mediate metastasis in patients, providing insights beyond a purely genetic analysis. We propose that this approach of screening many cell–ECM interactions, across many different heterogeneous cell lines, is predictive of in vivo behavior, and is much simpler, faster, and more economical than complex 3D environments or mouse models. We also propose that when specifically applied toward the question of tissue tropism in breast cancer, it can be used to provide insight into certain integrin subunits as therapeutic targets. We developed a high-throughput method to rapidly screen cell adhesion, motility, and growth factor responses on biomaterial surfaces. This approach is analogous to systems biology, relying on cell phenotypes in lieu of genetics. We used this technique to reveal patterns of phenotypes associated with breast cancer metastasis to possible tissue sites (bone, brain, lung). By comparing the phenotypic patterns between cell lines that metastasize to only one tissue site with heterogeneous cell lines, we provide the first method to connect in vitro phenotype to in vivo fate. This method is successful without genetic analysis, yet it also predicts outcomes related to integrin gene expression, potentially identifying new targets for tissue-specific metastasis.
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DOI：
10.1186/bcr1026
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Jenkins DE;Hornig YS;Oei Y;Dusich J;Purchio T
通讯作者：
Purchio T
DOI：
10.1083/jcb.200802081
发表时间：
2008-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fackler OT;Grosse R
通讯作者：
Grosse R
影响因子：
11.2
作者：
Barkan D;Kleinman H;Simmons JL;Asmussen H;Kamaraju AK;Hoenorhoff MJ;Liu ZY;Costes SV;Cho EH;Lockett S;Khanna C;Chambers AF;Green JE
通讯作者：
Green JE
DOI：
10.1158/1541-7786.mcr-12-0307
发表时间：
2012-11
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Karagiannis GS;Poutahidis T;Erdman SE;Kirsch R;Riddell RH;Diamandis EP
通讯作者：
Diamandis EP
ARTEMIN 与 TWIST1 协同作用促进 ER 阴性乳腺癌患者的转移和不良生存结果
DOI：
10.1186/bcr3054
发表时间：
2011
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Banerjee A;Wu ZS;Qian P;Kang J;Pandey V;Liu DX;Zhu T;Lobie PE
通讯作者：
Lobie PE