Abstract

Abstract Progression from a ductal carcinoma in situ (DCIS) to an invasive ductal carcinoma (IDC) involves changes in the surrounding extracellular matrix (ECM) fibril patterns before and during the development of ductal microinvasions, i.e., small cohorts of tumor cells that breach the duct and migrate through the stroma. We used a combination of mathematical modeling (with the hybrid agent-based model silicoDCIS) and advanced image analysis techniques applied to histological and fluorescent images in order to identify the rules of cell-ECM interactions that guide the emergence of various alignment patterns of the ECM fibrils. This includes the three tumor associated collagen signatures (TACS) previously observed in laboratory experiments. This integrated approach provides an in silico tool for testing biomechanical hypotheses of tumor cell-tumor matrix interactions. These findings can be compared to the patient histology samples and may help to define criteria for identification of DCIS to IDC transition and future development of new diagnostic methods. Citation Format: Katarzyna A. Rejniak, Sharan Poonja, Shreya Mathur, Mehdi Damaghi, Marilyn Bui. Dynamics of fibril collagen remodeling in early DCIS invasions: integrating in silico modeling and tumor histology [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B010.

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