Application of 3-D Microfluidic Models for Studying Mass Transport Properties of the Tumor Interstitial Matrix.

Alex Avendano,Jonathan W Song,Marcos Cortes-Medina

doi:10.3389/fbioe.2019.00006

Alex Avendano, Jonathan W Song + Show 1 more

Open Access

https://doi.org/10.3389/fbioe.2019.00006

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Abstract

The physical remodeling associated with cancer progression results in barriers to mass transport in the tumor interstitial space. This hindrance ultimately affects the distribution of macromolecules that govern cell fate and potency of cancer therapies. Therefore, knowing how specific extracellular matrix (ECM) and cellular components regulate transport in the tumor interstitium could lead to matrix normalizing strategies that improve patient outcome. Studies over the past decades have provided quantitative insights into interstitial transport in tumors by characterizing two governing parameters: (1) molecular diffusivity and (2) hydraulic conductivity. However, many of the conventional techniques used to measure these parameters are limited due to their inability to experimentally manipulate the physical and cellular environments of tumors. Here, we examine the application and future opportunities of microfluidic systems for identifying the physiochemical mediators of mass transport in the tumor ECM. Further advancement and adoption of microfluidic systems to quantify tumor transport parameters has potential to bridge basic science with translational research for advancing personalized medicine in oncology.

Highlights

Cancer has traditionally been described in terms of its molecular and genetic underpinnings, cellular heterogeneity, and network of signaling interactions during malignant progression (Hanahan and Weinberg, 2011)
Many solid tumor types, such as breast, pancreas, and liver, exhibit a desmoplastic response where stromal cells become hyperactivated leading to excessive extracellular matrix (ECM) production, growth of dense fibrotic tissue around the tumor (Trimboli et al, 2009; Kalluri, 2016), and subsequent tumor-promoting increases in mechanical stiffness (Leight et al, 2016; Reid et al, 2017)
To provide a balanced perspective, first we present a fundamental understanding of the physiological barriers to interstitial mass transport in tumors

Summary

Introduction

Cancer has traditionally been described in terms of its molecular and genetic underpinnings, cellular heterogeneity, and network of signaling interactions during malignant progression (Hanahan and Weinberg, 2011). APPLICATION OF MICROFLUIDIC MODELS FOR STUDYING TUMOR ECM TRANSPORT PROPERTIES With regards to quantifying transport within tumors, it is immensely challenging to independently specify concentration and pressure gradients and subsequently decouple the contributions of diffusion and convection.

Results

Conclusion