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

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.

Keywords: cellular microenvironment; extracellular matrix; microfabrication; therapeutic testing; tumor engineering.

Figure 1

Mass transport through the tumor interstitium. Once extravasated from the vascular space, molecules must cross the tumor interstitium, and eventually drain through the lymphatic vessels. The tumor interstitium is occupied by the interstitial matrix composed of fibrillar and non-fibrillar components such as collagen, glycosaminoglycans (GAGs), proteoglycans (PGs), and basement membrane produced by both cancer and stromal cells. This matrix imposes barriers to transport of molecules in tumors, contributing to a more hostile malignancy.

Figure 2

Characteristics of 3-D microfluidic platforms for studying transport in the tumor ECM. Microfluidic platforms possess the capacity to readily integrate these attributes to efficiently quantify transport parameters of the tumor ECM in vitro and study how they are affected by different cellular and matrix constituents.