JoVE：开发出新方法来检测细胞外液流动变化对肿瘤的影响

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有很多因素影响肿瘤浸润。尽管诸如遗传特征、组织类型和环境辐射之类的因素影响肿瘤转移和浸润，但是诸如细胞外液(extracellular fluid)流动之类的物理力量仍然是肿瘤浸润中一个知之甚少的组分。

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如今，一篇发表在<em>Journal of Visualized Experiments</em>期刊上的视频论文描述了一种新的方法，它能够允许研究人员研究和测试生长中肿瘤的微环境。这种技术是有价值的，因为它允许科学家们在体外检测由于细胞外液流动而引起的肿瘤浸润和更好地理解这些物理变化对肿瘤产生的影响。这项研究特别地关注一种被称作间质液(interstitial fluid)的细胞外液，其中间质液在组织中细胞之间流动。

当肿瘤生长时，它们促进肿瘤本身和周围组织内部的新血管生成。由于这些新血管存在漏洞，所以间质液压和间质液流动都发生增加。论文通讯作者Adrian Shieh博士注意到，当前的研究方法和治疗方法并不是针对这些生理变化的。在这项新研究中，这种新技术提供一种更好的方法来测量和理解间质液流动对肿瘤细胞的影响。

为了模拟这种生理过程，细胞被植入到胶原蛋白基质(collagen matrix)之中，然后给液体环境施加压力。这种压力导致细胞周围的液体流动，从而模拟生长中肿瘤的体内环境。这允许科学家们在更加接近于生理环境的培养系统中研究肿瘤生长和评价潜在的疗法对细胞的影响。

本文编译自<a href="http://medicalxpress.com/news/2012-07-fluid-cells-affects-tumors.html" target="_blank">How the fluid between cells affects tumors</a>
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<a title="" href="http://www.jove.com/video/4159/three-dimensional-cell-culture-model-for-measuring-effects" target="_blank">doi: 10.3791/4159</a>
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<br/><strong>Three-dimensional Cell Culture Model for Measuring the Effects of Interstitial Fluid Flow on Tumor Cell Invasion</strong><br/>


Alimatou M. Tchafa, Arpit D. Shah, Shafei Wang, Melissa T. Duong, Adrian C. Shieh

The growth and progression of most solid tumors depend on the initial transformation of the cancer cells and their response to stroma-associated signaling in the tumor microenvironment 1. Previously, research on the tumor microenvironment has focused primarily on tumor-stromal interactions 1-2. However, the tumor microenvironment also includes a variety of biophysical forces, whose effects remain poorly understood. These forces are biomechanical consequences of tumor growth that lead to changes in gene expression, cell division, differentiation and invasion3. Matrix density 4, stiffness 5-6, and structure 6-7, interstitial fluid pressure 8, and interstitial fluid flow 8 are all altered during cancer progression. Interstitial fluid flow in particular is higher in tumors compared to normal tissues 8-10. The estimated interstitial fluid flow velocities were measured and found to be in the range of 0.1-3 μm s-1, depending on tumor size and differentiation 9, 11. This is due to elevated interstitial fluid pressure caused by tumor-induced angiogenesis and increased vascular permeability 12. Interstitial fluid flow has been shown to increase invasion of cancer cells 13-14, vascular fibroblasts and smooth muscle cells 15. This invasion may be due to autologous chemotactic gradients created around cells in 3-D 16 or increased matrix metalloproteinase (MMP) expression 15, chemokine secretion and cell adhesion molecule expression 17. However, the mechanism by which cells sense fluid flow is not well understood. In addition to altering tumor cell behavior, interstitial fluid flow modulates the activity of other cells in the tumor microenvironment. It is associated with (a) driving differentiation of fibroblasts into tumor-promoting myofibroblasts 18, (b) transporting of antigens and other soluble factors to lymph nodes 19, and (c) modulating lymphatic endothelial cell morphogenesis 20. The technique presented here imposes interstitial fluid flow on cells in vitro and quantifies its effects on invasion (Figure 1). This method has been published in multiple studies to measure the effects of fluid flow on stromal and cancer cell invasion 13-15, 17. By changing the matrix composition, cell type, and cell concentration, this method can be applied to other diseases and physiological systems to study the effects of interstitial flow on cellular processes such as invasion, differentiation, proliferation, and gene expression.

<br/>来源：生物谷

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