[Materialstoday] Engineering cancer microenvironments for in vitro 3-D tumor models
The natural microenvironment of tumors is composed of extracellular matrix (ECM), blood vasculature, and supporting stromal cells. The physical characteristics of ECM as well as the cellular components play a vital role in controlling cancer cell proliferation, apoptosis, metabolism, and differentiation. To mimic the tumor microenvironment outside the human body for drug testing, two-dimensional (2-D) and murine tumor models are routinely used. Although these conventional approaches are employed in preclinical studies, they still present challenges. For example, murine tumor models are expensive and difficult to adopt for routine drug screening. On the other hand, 2-D in vitro models are simple to perform, but they do not recapitulate natural tumor microenvironment, because they do not capture important three-dimensional (3-D) cell–cell, cell–matrix signaling pathways, and multi-cellular heterogeneous components of the tumor microenvironment such as stromal and immune cells. The three-dimensional (3-D) in vitro tumor models aim to closely mimic cancer microenvironments and have emerged as an alternative to routinely used methods for drug screening. Herein, we review recent advances in 3-D tumor model generation and highlight directions for future applications in drug testing.
Waseem Asghar1, 2, 5, , , Rami El Assal1, 5, Hadi Shafiee3, Sharon Pitteri4, Ramasamy Paulmurugan4, Utkan Demirci1, 3, 4, , 1 Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratories, Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford School of Medicine, Stanford University, Palo Alto, CA 94304, USA 2 Department of Computer Engineering & Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA 3 Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratories, Division of Biomedical Engineering, Division of Infectious Diseases, Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA 4 Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford School of Medicine, Stanford University, Palo Alto, CA 94304, USA Available online 10 June 2015