Editors' ChoiceCancer

Engineering tumors by rolling sheets

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Science Translational Medicine  16 Dec 2015:
Vol. 7, Issue 318, pp. 318ec216
DOI: 10.1126/scitranslmed.aad9008

A major challenge in cancer research has been the lack of experimental models that are easy to use and can fully recapitulate the biology of tumors. This is especially true for hypoxia and cancer metabolism studies, where existing two- and three-dimensional (3D) tissue cultures fail to capture many of the important properties of the human condition, notably the hypoxic gradient. Although in vivo mouse cancer models can recapitulate the biology, they are very challenging to study. To address this, Rodenhizer et al. created a 3D tumor model that can recapitulate the hypoxic gradient and metabolism gradient of human tumors.

The authors engineered the 3D tumor model [tumor roll for analysis of cellular environment and response (TRACER)] by first generating a biocomposite strip consisting of tumor cells, collagen I, and cellulose. The strip was then rolled around a 6-mm metallic core to form a tumor. The entire tumor was then submerged in culture medium. The authors demonstrated that TRACER closely mimics the gradients seen in in vivo tumors, where oxygen and nutrients have to diffuse to reach cells inside the tumor. In addition, the investigators showed that cells at different parts of the gradient can be analyzed by unrolling the strips, allowing spatial mapping of cell metabolism. The authors also used this model to identify previously unknown metabolic responses to hypoxia.

Although these results are promising, the study also has several limitations. First, the scaffold materials of collagen and cellulose differ from those of the naturally occurring tumor microenvironment, which is known to be critically important in cancer biology. In addition, the presence of the scaffold sheet within TRACER disrupts some of the cell-to-cell interactions, which can affect overall tumor biology. Last, the TRACER model does not reflect organ specificity, a key attribute of human tumors. Despite these limitations, the described TRACER model represents an important tool in cancer biology research. It can not only reveal new biology as described in this work, but also be used to screen for therapeutic agents that target hypoxia and/or cancer metabolism. This research may also inspire further development of engineered tumors that more accurately reproduce the human condition.

D. Rodenhizer et al., A three-dimensional engineered tumour for spatial snapshot analysis of cell metabolism and phenotype in hypoxic gradients. Nat. Mater. 10.1038/nmat4482 (2015). [Abstract]

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