Collagen organization and density can have a profound effect on the behavior of breast cancer cells.  Using second harmonic generation (SHG), the structure of collagen in intact mammary mouse mammary glands can be visualized.  In collaboration with the Keely Lab, a metastatic collagen signature (TACS3) has been identified leading to useful characterization of breast tissue and tumors.

Tissue microenvironment, especially collagen abundance and organization, plays an important role in mammary cell behavior.  Humans with collagen-dense breast tissue have a greater than four-fold increased risk of breast cancer.  Multiphoton laser scanning microscopy (MPLSM) can be utilized to elucidate the impact of collagen organization on tumor progression.  Multiphoton excitation (MPE) and second harmonic generation (SHG) are used to image cellular structure and collagen organization in unfixed, intact, and non-stained glands at depths of up to 440 nm.  Using MPE/SHG imaging, three tumor-associated collagen signatures (TACS1-3) have been identified denoting changes in collagen organization throughout progression of tumors from nonpalpable (1) to non-invasive (2) to metastatic (3).  These imaging techniques can be used to characterize breast tumors in animal models and, in the future, human tumor biopsies, aiding in tumor detection and creation of treatment plans. In collaboration with the Keely Laboratory and others, LOCI is actively developing computational approaches such as curvelets to measure collagen and new optical techniques to use collagen as a clinical biomarker.