Tumour-cell invasion and migration: diversity and escape mechanisms

Abstract

The process of tumour-cell invasion and metastasis is conventionally understood as the migration of individual cells that detach from the primary tumour, enter lymphatic vessels or the bloodstream and seed in distant organs. Novel imaging techniques (both in vitro and in vivo), together with re-evaluation of histopathological pattern formation in tumours, have provided a detailed view of cellular and molecular migration dynamics in cancer cells. Cancer cells disseminate from the primary tumour either as individual cells, using amoeboid- or mesenchymal-type movement, or as cell sheets, strands and clusters using collective migration. Cancer-cell migration is typically regulated by integrins, matrix-degrading enzymes, cell–cell adhesion molecules and cell–cell communication. Cancer therapeutics designed to target adhesion receptors or proteases have not yet been show to be effective in clinical trials. This might be due to the fact that the cancer cell's migration mechanisms can be reprogrammed, allowing it to maintain its invasive properties via morphological and functional de-differentiation. These adaptation responses include the epithelial–mesenchymal transition (EMT), the mesenchymal–amoeboid transition (MAT) and the collective–amoeboid transition (CAT). Further studies are required to identify the factors that are involved in each type of cell migration, as well as related escape strategies that are used by cancer cells after pharmacotherapeutic intervention.