BME PhD Proposal Seminar: Kathleen Burke

SHG Analysis of Collagen Structure throughout Breast Cancer Progression & Metastasis

Supervised by Dr. Edward Brown

Abstract:

With the increased capabilities of early detection and treatment of breast cancer, mortality rates due to the primary tumor have decreased, and currently 90% of cancer mortality is a result of metastatic events. In the process of metastasis tumor cells must pass through the tumor extracellular matrix, and matrix structure has been shown to predict metastatic outcome. Consequently we are interested in understanding the structure and function of the tumor extracellular matrix with the ultimate goal of improving our ability to predict and prevent breast tumor metastasis. Second Harmonic Generation (SHG) is a scattering phenomenon in which two photons are combined into one emission photon by a non-centrosymmetric scattering material such as collagen fibrils. It has been shown that qualitative morphological analysis of collagen SHG images can be used to predict metastatic potential of a primary breast tumor. In ovarian cancer the scattering directionality, as defined by the F/B ratio was used to differentiate between healthy and cancerous tissue by directly capturing forward and backward propagating photons.

This research will provide a method of quantitative monitoring of the F/B ratio alongside other intrinsic signals throughout tumor progression, to increase understanding of the cause and effect of extracellular matrix changes in the stroma. To accomplish this goal, we will propose a four part study to determine the structural changes occurring throughout progression in human samples and investigate the causes of these changes through the use of electron microscopy, collagen gels, and mouse models. In the first Aim we will use SHG imaging to study the progression of the tumor extracellular matrix throughout the development of the primary tumor. In Aim 2 we will identify the physical collagen changes that correspond to the observed F/B progression. For Aim 3 we will evaluate the relationship between collagen F/B and tumor locomotion. And in Aim 4 we will investigate the evolution versus predetermined nature of the collagen structure during N stage progression. Breast cancer forms highly diverse tumors characterized by their location in the tissue, their receptors, and other histological features. By enhancing the capabilities of F/B measurements of SHG, this increases the understanding of tumor metastasis, may improve diagnostic capabilities, and may increase potential for future treatment through a better understanding of the role extracellular matrix changes play in the tumor metastasis.