有很多因素影響腫瘤浸潤(rùn),。盡管諸如遺傳特征,、組織類(lèi)型和環(huán)境輻射之類(lèi)的因素影響腫瘤轉(zhuǎn)移和浸潤(rùn)，但是諸如細(xì)胞外液(extracellular fluid)流動(dòng)之類(lèi)的物理力量仍然是腫瘤浸潤(rùn)中一個(gè)知之甚少的組分,。
如今,，一篇發(fā)表在Journal of Visualized Experiments期刊上的視頻論文描述了一種新的方法，它能夠允許研究人員研究和測(cè)試生長(zhǎng)中腫瘤的微環(huán)境。這種技術(shù)是有價(jià)值的,，因?yàn)樗试S科學(xué)家們?cè)隗w外檢測(cè)由于細(xì)胞外液流動(dòng)而引起的腫瘤浸潤(rùn)和更好地理解這些物理變化對(duì)腫瘤產(chǎn)生的影響,。這項(xiàng)研究特別地關(guān)注一種被稱作間質(zhì)液(interstitial fluid)的細(xì)胞外液，其中間質(zhì)液在組織中細(xì)胞之間流動(dòng),。
當(dāng)腫瘤生長(zhǎng)時(shí),，它們促進(jìn)腫瘤本身和周?chē)M織內(nèi)部的新血管生成。由于這些新血管存在漏洞,，所以間質(zhì)液壓和間質(zhì)液流動(dòng)都發(fā)生增加,。論文通訊作者Adrian Shieh博士注意到，當(dāng)前的研究方法和治療方法并不是針對(duì)這些生理變化的,。在這項(xiàng)新研究中,，這種新技術(shù)提供一種更好的方法來(lái)測(cè)量和理解間質(zhì)液流動(dòng)對(duì)腫瘤細(xì)胞的影響。
為了模擬這種生理過(guò)程,，細(xì)胞被植入到膠原蛋白基質(zhì)(collagen matrix)之中,，然后給液體環(huán)境施加壓力。這種壓力導(dǎo)致細(xì)胞周?chē)囊后w流動(dòng),，從而模擬生長(zhǎng)中腫瘤的體內(nèi)環(huán)境,。這允許科學(xué)家們?cè)诟咏咏谏憝h(huán)境的培養(yǎng)系統(tǒng)中研究腫瘤生長(zhǎng)和評(píng)價(jià)潛在的療法對(duì)細(xì)胞的影響。(生物谷：Bioon.com)
本文編譯自How the fluid between cells affects tumors
doi: 10.3791/4159
PMC:
PMID:
Three-dimensional Cell Culture Model for Measuring the Effects of Interstitial Fluid Flow on Tumor Cell Invasion
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.
