Second Harmonic Generation in tumors
A forward scattering/backwards scattering ratio image of collagen (600 microns accross) in excised and sectioned 4T1 murine mammary adenocarcinoma. The forwards/backwards ratio (F/B) provides insight into the spatial organization of collagen fibers within the tumor.
Tumor metastasis is a critical event in breast cancer progression, hence novel approaches to predict and prevent metastasis would be of great clinical value. We and others have recently found that a novel property within tumors - the extent and nature of the ordering of collagen fibers - has significant influence on the process of tumor metastasis.
This property can be studied via an optical process called Second Harmonic Generation (SHG), which is very sensitive to the order, or organization, of matter. In tumors, we and others have shown that SHG is caused primarily by collagen, and is sensitive to the extent to which collagen is bundled into fibers, the way the fibers are bundled together, the thickness of the fibers, and other structural properties.
SHG can be used in microscopes to make high-resolution images of tumor collagen which reveal many of these properties. These images have revealed that tumor cells use
roads of ordered (SHG-producing) collagen to move rapidly throughout a tumor, to approach and enter blood vessels, and to escape the tumor mass. We are currently studying which cells in the tumor are contributing to the construction of these
roads and what signaling molecules they are using to do this. In the future this may lead to new treatments for breast cancer which will disrupt these
roads and hence prevent, or at least slow down, the tumor cells from metastasizing.