Second Harmonic Generation in tumors

Project Collaborators:

Dr. Bradley Turner
Dr. Vinay Abhyankar 

A forward scattering/backwards scattering ratio image of
collagen (600 microns across) 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 have recently found that a novel property within tumors - the internal structure of collagen fibers – can provide significant information about 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 fibrillar 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 collagen to move rapidly throughout a tumor, to approach and enter blood vessels, and to escape the tumor mass. We are currently studying how to exploit these optical signals to make useful predictions about the metastatic process, as well as 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 prognostic methods for predicting a patient’s metastatic future, as well as treatments for breast cancer which will disrupt these roads and hence prevent, or at least slow down, the tumor cells from metastasizing.

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