Modeling Tumor Microenvironments In Vitro

Abstract

Tumor progression depends critically upon the interactions between the tumor cells and their microenvironment. The tumor microenvironment is heterogeneous and dynamic; it consists of extracellular matrix, stromal cells, immune cells, progenitor cells, and blood and lymphatic vessels. The emerging fields of tissue engineering and microtechnologies have opened up new possibilities for engineering physiologically relevant and spatially well-defined microenvironments. These in vitro models allow specific manipulation of biophysical and biochemical parameters, such as chemical gradients, biomatrix stiffness, metabolic stress, and fluid flows; thus providing a means to study their roles in certain aspects of tumor progression such as cell proliferation, invasion, and crosstalk with other cell types. Challenges and perspectives for deconvolving the complexity of tumor microenvironments will be discussed. Emphasis will be given to in vitro models of tumor cell migration and invasion.

Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed “in vivo”

“…Based on this background, a variety of innovative "in vitro" technologies are currently being developed to provide the scientific community with advanced models potentially overcoming limitations of current assays and eventually improving their predictive performance [4,5]. A series of studies have underlined that culture in bi-dimensional (2D) or tri-dimensional (3D) systems differentially affects sensitivity of cancer cells to compounds used in cancer treatment [6e9] or to immune effector cells specific for human tumor associated antigens [10].…”

Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

“…This is partly due to the high cost of developing a new anti-cancer drug, as well as the need to better understand cancer development and the tumour microenvironment (TME), including the roles of inflammation, different effectors and suppressors of immune responses, the heterogeneity of tumour stroma, and the function of tumour vasculature. To make significant improvements in cancer therapy, it is necessary to develop more effective approaches to screen anti-cancer drug leads and to have a better understanding of TME using advanced technologies, including the organs-on-chips technology [1][2][3][4][5].…”

Interstitial flows promote amoeboid over mesenchymal motility of breast cancer cells revealed by a three dimensional microfluidic model

“…Recently, microfluidic models have emerged for studying effects of interstitial flows on tumor cell invasion because of their compatibility with optical microscope, making it possible to follow single-cell dynamics in both time and space 35-37 . In addition, microfluidic models have the advantage of providing well controlled microenvironments, such as fluid flows within a 3D ECM 38 . Current microfluidic models have revealed that flow-guided cell migration depended on a number of critical parameters within the tumor microenvironment, including chemokine receptors, matrix stiffness, cell density, and flow rates 35, 36, 39 .…”