Exploring the Role of Collagen Structure in Breast Cancer Metastatic Progression

描述（由申请人提供）：随着乳腺癌早期检测和治疗能力的提高，原发肿瘤导致的死亡率下降，目前90%的癌症死亡是转移事件的结果。在转移过程中，肿瘤细胞必须通过肿瘤细胞外基质，基质结构已被证明可以预测转移结果。因此，我们有兴趣了解肿瘤细胞外基质的结构和功能，最终目的是提高我们预测和预防乳腺肿瘤转移的能力。二次谐波产生（SHG）是一种由非中心对称散射材料（如胶原纤维）将两个光子组合成一个发射光子的散射现象。已有研究表明，胶原SHG图像的定性形态学分析可用于预测原发性乳腺肿瘤的转移潜力。在卵巢癌中，散射方向性，由前向散射与后向散射SHG发射的比值（“F/B比值”）定义，通过直接捕获前向和后向传播的光子来区分健康组织和癌组织。我们以前的工作已经从人类肿瘤活检中表明，F/B比率可以用来区分更容易转移到淋巴结的乳腺肿瘤。本研究计划将由两部分组成，将利用定量监测F/B比率的方法来增加我们对细胞外基质变化在整个转移过程中在基质中的作用的理解。本提案的第一个具体目的是通过胶原凝胶操作来评估胶原F/B与肿瘤运动之间的关系。目标2的重点是研究资产/资产比率的时间行为。这两种目的还将结合电子显微镜，并确定与观察到的F/B进展相对应的胶原蛋白的物理变化。乳腺癌形成高度多样化的肿瘤，其特征在于其在组织中的位置、受体和其他组织学特征。这项工作的目的是利用SHG F/B测量的能力来提高我们对细胞外基质变化在肿瘤转移中的作用的理解，从而提高治疗和诊断能力。

DESCRIPTION (provided by applicant): 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 ratio of forward-scattered to backward-scattered SHG emission (the "F/B ratio") was used to differentiate between healthy and cancerous tissue by directly capturing forward and backward propagating photons. Our work has previously shown from human tumor biopsies that the F/B ratio can be used to distinguish breast tumors that are more metastatic to the lymph nodes. This research proposal will be composed of two parts, which will utilize methods of quantitatively monitoring of the F/B ratio to increase our understanding of the role of extracellular matrix changes in the stroma throughout metastatic progression. The first specific Aim of this proposal is to evaluate the relationship between collagen F/B and tumor locomotion through collagen gel manipulation. The focus of Aim 2 is to investigate the temporal behavior of the F/B ratio. Both aims will also incorporate electron microscopy and to identify the physical collagen changes that correspond to the observed F/B progression. Breast cancer forms highly diverse tumors characterized by their location in the tissue, their receptors, and other histological features. Th goal of this work is to utilize the capabilities of SHG F/B measurements to improve our understanding of the role extracellular matrix changes play in the tumor metastasis and thereby improve treatment and diagnostic capabilities.