Understanding tissue architecture and physical and chemical reciprocity between cells and their microenvironment provides vital insights into key events in cancer metastasis, such as cell migration through three-dimensional (3D) extracellular matrices. Yet, many mechanistic details associated with metastasis remain elusive due to the difficulty of studying cancer cells in relevant 3D microenvironments. Recently, optical imaging has facilitated the direct observation of single cells as they undertake fundamental steps in the metastatic processes. Optical imaging is also providing novel 'optical biomarkers' with diagnostic potential that are linked to cell-motility pathways associated with metastasis, and these can to help guide new approaches to cancer diagnosis and therapy. Here we present recent advances in one subclass of optical imaging of particular promise for cellular imaging - multiphoton microscopy - that can be used to improve the detection of malignant cells as well as advance our understanding of the cell biology of cancer metastasis. © 2009 Elsevier Ltd. All rights reserved.
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