Imaging Invasion and Metastasis In Vivo

Abstract

Current clinical imaging methods for breast cancer do not visualize individual cells moving in the primary tumor microenvironment. In animal models of cancer, confocal imaging using multiphoton excitation provides reduced photobleaching, deeper imaging into thick specimens, and observation of some extracellular matrix fibers. Individual cells expressing fluorescent proteins such as GFP can be observed in order to evaluate the mechanisms of tumor cell invasion and metastasis. Tumor cells in vivo can show orientation towards blood vessels, and rapid movement along extracellular matrix fibers. To directly measure tumor cell invasion in the primary tumor in response to imposed gradient of growth factors, needles containing EGF or CSF-1 have been found to stimulate invasion into the needle. Transgenic models of breast cancer which have lost expression of CSF-1 show reduced invasiveness and metastasis. These results indicate that tumor cells can collaborate with macrophages during invasion. Such paracrine interactions between epithelial cells and macrophages likely reflect interactions that occur during ductal outgrowth in normal mammary gland development. The combination of in vivo imaging with genetic manipulation of xenograft and transgenic models of breast cancer will enable direct examination of mechanisms of invasion and metastasis.