In vitro models of tumor vessels and matrix: Engineering approaches to investigate transport limitations and drug delivery in cancer

Abstract

Tumor-stroma interactions have emerged as critical determinants of drug efficacy. However, the underlying biological and physicochemical mechanisms by which the microenvironment regulates therapeutic response remain unclear, due in part to a lack of physiologically relevant in vitro platforms to accurately interrogate tissue-level phenomena. Tissue-engineered tumor models are beginning to address this shortcoming. By allowing selective incorporation of microenvironmental complexity, these platforms afford unique access to tumor-associated signaling and transport dynamics. This review will focus on engineering approaches to study drug delivery as a function of tumor-associated changes of the vasculature and extracellular matrix (ECM). First, we review current biological understanding of these components and discuss their impact on transport processes. Then, we evaluate existing microfluidic, tissue engineering, and materials science strategies to recapitulate vascular and ECM characteristics of tumors, and finish by outlining challenges and future directions of the field that may ultimately improve anti-cancer therapies.

Breast cancer-derived extracellular vesicles stimulate myofibroblast differentiation and pro-angiogenic behavior of adipose stem cells

“…Finally, future studies will need to test whether the detected differences in TEV-mediated changes of ASC proangiogenic capability contribute to the formation of leaky and dilated vessels found in tumors[66]. Such studies can be performed in vivo , but would also benefit from microfluidic platforms in which perfusable endothelialized channels can be embedded into ASC-seeded collagen scaffolds and allow generating insights into how TEV-treated ASCs contribute to remodeling of the tumor vasculature[67,68]. …”

Three-dimensional in vitro tumor models for cancer research and drug evaluation

“…During cancer progression and metastasis, malignant cells maintain their close interactions with surrounding cells and the stromal extracellular matrices (ECM) (Fig. 1) (DelNero et al, 2013; Hanahan and Weinberg, 2011; Infanger et al, 2013; Nyga et al, 2011; Seo et al, 2013). Numerous stromal cells, including endothelial cells of the blood and lymphatic circulation, stromal fibroblasts, and innate and adaptive infiltrating immune cells together comprise the complex tumor microenvironment (Hanahan and Weinberg, 2011; Joyce and Pollard, 2009; Koontongkaew, 2013).…”

“…The 3D organization of the tumor mass, as well as the associated stroma, fundamentally alters the diffusion profile for drugs, both through the cell-cell contacts and cell-matrix interactions (Chauhan et al, 2011). Detailed descriptions on physicochemical properties of native tumor microenvironments including cell-cell and cell-matrix interactions, tissue structure and mechanics, as well as juxtacrine and soluble factor signaling, can be found in recent reviews by Fischbach and coworkers (DelNero et al, 2013; Infanger et al, 2013; Seo et al, 2013). …”

DNA Aptamers for the Characterization of Histological Structure of Lung Adenocarcinoma

“…Tumor vessels are leaky, fenestrated, tortuous, dilated, and have chaotic irregular hierarchy branching patterns 37 . Recent studies have shown that endothelial cells lining the walls of blood vessels may appear modified as a result of reprogramming fibroblasts via SET-like protein and VEGF 38 .…”