Abstract A32: Tumor-matrix tnteractions in early ductal invasions: Integrating histology imaging with computational modeling

Abstract

Abstract Progression from a ductal carcinoma in situ (DCIS) to an invasive tumor is a major step initiating a devastating and often lethal metastatic cascade. One sentinel event that initiate this process is the development of ductal microinvasions, i.e., small cohorts of tumor cells that breach the basement membrane surrounding the duct, and migrate through the extracellular matrix (ECM). This process is difficult to reproduce experimentally and investigate in a fully controlled way. However, mathematical modeling based on physical principles and medical imaging can shed light on interactions between tumor cells and the surrounding stroma during the spread of microinvasions. We used a combination of advanced image analysis techniques applied to patients' histology data, that include both tissue regions and single cells segmentation, with multi-factorial classification to extract feature data which identifies specific properties of individual tumor cells inside the duct and on the invasive front. These histology-based quantitative data were then used to calibrate a hybrid agent-based mathematical model of DCIS-ECM interactions that takes into account both individual tumor cells and the underlying ECM fibril structure. The model was employed in a computational simulation study to delineate physical properties of the matrix fibers that can facilitate and/or prevent formation and progression of ductal microinvasions. Our integrated approach incorporating medical imaging and computational modeling, allowed us to predict the dynamics of emerging ductal microinvasions that are consistent with the observed clinical data. We showed how changes in the local microenvironmental niche near the DCIS edge leads to initiation of ductal microinvasions. We identified physical properties of the matrix that can facilitate or prevent the progression of such microinvasions. Our methods also provide a tool for quantifying morphological and immunohistochemical properties of individual cells within the mammary ducts and ductal microinvasion, as well as a tool for testing biomechanical hypotheses of tumor cell-tumor matrix interactions. These findings can be directly compared to the patient histology samples and can lead to development of new prognostic methods and therapeutic interventions by targeting the tumor preinvasive niche. Citation Format: Katarzyna A. Rejniak, Mark C. Lloyd, Agnieszka Kasprzak, Marilyn Bui. Tumor-matrix tnteractions in early ductal invasions: Integrating histology imaging with computational modeling. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A32.