Abstract
The behavior of cells within tissues is controlled by interactions with soluble signals, neighboring cells, and the surrounding extracellular matrix (ECM); collectively, these interactions constitute the cellular microenvironment. While normal tissue homeostasis can suppress outgrowth of cells with oncogenic mutations, progression to malignant cancer is associated with alterations in the cellular microenvironment that facilitate cancer cell proliferation, detachment from adjacent cells, and penetration of the surrounding ECM [1]. Several recent studies have provided new insight into how microenvironmental signals combine to facilitate tissue invasion of individual cancer cells [2, 3]. In the first, careful monitoring of the invasion process through timelapse microscopy was used to evaluate the behavior of normal and cancerous breast tissue explants cultured in three-dimensional (3D) ECM [3]. These studies revealed that sustained cellular invasion occurred only when cells were cultured in ECM composed of stromal collagen, and also that acquisition of the invasive phenotype was relatively rare, occurring only in a very small fraction of the cells in the explant. Furthermore, invasion was found to occur preferentially at regions that protruded from the tissue fragments, and was preceded by loss of cellcell adhesions [3]. These studies indicated that cellular invasion required a combination of the correct tissue structural orientation as well as specific cell-cell and cellECM interactions. To define how cell-cell and cell-ECM interactions
Highlights
The behavior of cells within tissues is controlled by interactions with soluble signals, neighboring cells, and the surrounding extracellular matrix (ECM); collectively, these interactions constitute the cellular microenvironment
To define how cell-cell and cell-ECM interactions are integrated in a tissue context, Boghaert et al [2] used microengineered tissues, created by embedding single breast cancer cells within a surrogate duct structure composed of nonmalignant mammary epithelial cells in 3D collagen molds (Figure 1A,B)
Computational modeling and experimental microbead displacement studies revealed that these regions showed the highest endogenous mechanical stress; investigation of different tissue morphologies and orientations revealed that tissue stress was induced by contraction of the surrogate ducts within 3D collagenous matrix (Figure 1D-F)
Summary
The behavior of cells within tissues is controlled by interactions with soluble signals, neighboring cells, and the surrounding extracellular matrix (ECM); collectively, these interactions constitute the cellular microenvironment. To define how cell-cell and cell-ECM interactions are integrated in a tissue context, Boghaert et al [2] used microengineered tissues, created by embedding single breast cancer cells within a surrogate duct structure composed of nonmalignant mammary epithelial cells in 3D collagen molds (Figure 1A,B). This model system was used to parse out the tissue-based biophysical characteristics that control cancer cell invasion.
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