Modeling tumor microenvironments in vitro.

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.