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BME Ph.D. Thesis Defense Seminar

K-207 Med Center 2-6408

"Second Harmonic Generation to Study Breast Cancer Progression and Predict Metastatic Potential"

Presented by: Kathleen Burke
Supervised by: Professor Edward Brown

Abstract: 90% of cancer mortality is a result of metastasis of a tumor to a secondary location. During metastasis tumor cells interact with the tumor extracellular matrix. Collagen, a key component of the extracellular matrix (ECM), produces an intrinsic optical signal caused by the scattering phenomenon Second harmonic generation (SHG), which allows us to monitor changes in the tumor ECM throughout tumor progression. My research uses SHG imaging of breast tumor models to better understand the role ECM changes play in tumor metastasis. The first aim in this thesis showed a series of changes in SHG signals that occur throughout ductal and lobular carcinoma progression, revealing a complex evolution of the matrix with grade and stage. These results suggested that in invasive ductal carcinoma tumors there might be a significant relationship between the tumor collagen microstructure (which affects SHG) and its metastatic potential. In the second aim we explored the possibility that the tumor collagen microstructure may provide additional information on tumor metastatic potential and future patient outcomes.  Results showed that our SHG measurements can predict metastasis-free survival and overall survival rates in estrogen receptor positive, node-negative patients. These measurements are also related to overall survival in stage I colorectal adenocarcinoma, pointing to a possible shared mechanism of metastasis linking the collagen microstructural changes and tumor metastatic capacity. In the final aim we transitioned to a “clean” environment of collagen gels to evaluate the possibility that the detected changes in collagen microstructure affect individual tumor cell motility. This work revealed a significant relationship between SHG measures of collagen gel microstructure and the total distance traveled by cells moving on the gels. These experiments suggest that collagen microstructure influences tumor cell motility and that the observed relationship between metastasis and primary tumor SHG signatures is due at least in part to an effect of the structure on tumor cell motility.