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Research Papers

Modeling Tumor Microenvironments In Vitro

[+] Author and Article Information
Mingming Wu

Department of Biological
and Environmental Engineering,
Cornell University,
Ithaca, NY 14853

Melody A. Swartz

Institute of Bioengineering and
Institute for Experimental
Cancer Research (ISREC),
School of Life Sciences,
École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland

Contributed by the Bioengineering Division of ASME for publication in the Journal of Biomechanical Engineering. Manuscript received October 16, 2013; final manuscript received December 28, 2013; accepted manuscript posted January 9, 2014; published online February 5, 2014. Editor: Victor H. Barocas.

J Biomech Eng 136(2), 021011 (Feb 05, 2014) (7 pages) Paper No: BIO-13-1492; doi: 10.1115/1.4026447 History: Received October 16, 2013; Revised December 28, 2013; Accepted January 09, 2014

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.

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Topics: Tumors
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Figures

Grahic Jump Location
Fig. 1

Tumor microenvironments and the corresponding in vitro models. (a) Single cell embedded in a 3D biomatrix. The cell is pulling on the collagen fiber. Dots represent adhesion molecules. (b) A microfabricated cell force sensor. The bending of the micropillars is used to report the cellular force. Graph is adapted from [60] and copyright of the Proceedings of National Academy of Sciences. (c) Molecular gradients via paracrine signaling. (d) A modified Boyden Chamber assay for tumor cell invasion and transendothelial migration under interstitial flow conditions. Graph is adapted from [22] with permission from American Association for Cancer Research. (e) Illustration of interstitial flow near a lymphatic vessel and tumor cell intravasation. (f) Microfluidic model for studies of tumor cell intravasation in the presence of a flow. (Graph is adapted from [41]. with permission from the Royal Society of Chemistry.)

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