Cell migration/invasion assays and their application in cancer drug discovery

Abstract

Invasive capacity is the single most important trait that distinguishes benign from malignant lesions. Tumour cells, during intravasation and extravasation of blood and lymphatic channels and when establishing colonies at secondary sites, must move through tissue boundaries that normal adult cells (other than, for example activated leukocytes) do not cross. Similar mechanisms are also utilised by activated endothelial cells during the generation of new blood vessels that enable the sustained growth and dissemination of tumours. It is now increasingly recognised that these processes--cell motility and invasion--might provide a rich source of novel targets for cancer therapy and that appropriate inhibitors may restrain both metastasis and neoangiogenesis. This new paradigm demands screening assays that can rapidly and quantitatively measure cell movement and the ability to traverse physiological barriers. We also need to consider whether simple reductionist in vitro approaches can reliably model the complexity of in vivo tumour invasion/neoangiogenesis. There are both opportunities and challenges ahead in developing a balanced portfolio of assays that will be able to evaluate accurately and finally deliver novel anti-invasive agents with therapeutic potential for clinical use.