Intravital imaging and cell invasion

The main cause of cancer treatment failure is the invasion of normal tissues by cancer cells that have migrated from a primary tumor. An important obstacle to understanding cancer invasion has been the inability to acquire detailed, direct observations of the process over time in a living system. Intravital imaging, and the rodent dorsal skinfold window chamber in particular, were developed several decades ago to address this need. However, it is just recently, with the advent of sophisticated new imaging systems such as confocal and multiphoton microscopy together with the development of a wide range of fluorescent cellular and intracellular markers, that intravital methods and the window chamber have acquired powerful new potential for the study of cancer cell invasion. Moreover, the interaction of various cell signaling pathways with the integrin class of cell surface receptors has increasingly been shown to play a key role in cancer invasion. The window chamber in combination with integrin-knockout rodent models, integrin-deficient tumor cell lines, and integrin antagonists, allows real-time observation of integrin-mediated cancer invasion and angiogenesis. The present review outlines the history, uses, and recent methods of the rodent dorsal skinfold window chamber. The introduction of labeled tumor cells into the chamber is described, and imaging of tumors and angiogenic vessels within chambers using standard brightfield, confocal, and multiphoton microscopy is discussed in detail, along with the presentation of sample images.