Abstract
The advent of co-culture approaches has allowed researchers to more accurately model the behaviour of epithelial cells in cell culture studies. The initial work on epidermal modelling allowed the development of reconstituted epidermis, growing keratinocytes on top of fibroblasts seeded in a collagen gel at an air-liquid interface to generate terminally differentiated 'skin equivalents'. In addition to developing ex vivo skin sheets for the treatment of burns victims, such cultures have also been used as a means of investigating both the development and repair of the epidermis, in more relevant conditions than simple two-dimensional culture, but without the use of animals. More recently, by varying the cell types used and adjusting the composition of the matrix components, this physiological system can be adapted to allow the study of interactions between tumour cells and their surrounding stroma, particularly with regards to how such interactions regulate invasion. Here we provide a summary of the major themes involved in tumour progression and consider the evolution of the approaches used to study cancer cell behaviour. Finally, we review how organotypic models have facilitated the study of several key pathways in cancer development and invasion, and speculate on the exciting future roles for these models in cancer research.
Highlights
Tumourigenesis is a complex process during which tumour cells acquire a sequence of mutations in genes that directly or indirectly control processes such as cell proliferation, survival, migration and invasion
It is becoming increasingly clear that, despite the accrual of advantageous mutations occurring in the cancer cells, cells in the stroma can play a critical role in mediating tumour growth and progression
Simple cell culture studies have given us amazing insight into the cell and molecular biology underpinning cancer cell behaviour, researchers are increasingly turning to more complex and physiologically relevant cell culture models, where more than one cell type is present, to better understand the nature of cancer
Summary
Tumourigenesis is a complex process during which tumour cells acquire a sequence of mutations in genes that directly or indirectly control processes such as cell proliferation, survival, migration and invasion. Breast cancer 3-D cultures have been used to investigate gene expression profiles [89,91] and to study the interaction of human epithelial cells with their microenvironment, including fibroblasts, myofibroblasts and ECM [86]. Future studies Organotypic cultures have shown that it is possible to recreate, in the laboratory, a histologically similar tissue equivalent for several tissue types, using just two cell types and a matrix Such relatively basic models are simple to prepare, taking less than 2 weeks to grow, and can be used to study cell migration and invasion with relative ease. Understanding the biological relevance of target molecules, using RNAi-based approaches, will be possible for the cancer cells themselves and the stromal cells with which they are associated This is of great importance given the growing acceptance of the critical role the microenvironment plays in tumour progression. Large-scale functional RNAi screens will be possible, together with more conventional small molecule screening, in the hope that future cell culture studies, based on more physiologically representative models, will be more readily translated into clinically relevant findings
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