Abstract LT017: ECM mechanical and metabolic architecture during early ductal invasions: integrating in silico modeling, histology-based machine learning and mechanobiology

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) leading to irreversible changes in tumor and stromal architecture. We used a combination of advanced image analysis techniques applied to patients’ histology data to extract features which identify specific properties of individual tumor cells inside the duct and on the invasive front. By integrating these histology-based data with a hybrid agent-based mathematical model, we investigated the biomechanical interactions between the cells and the ECM fiber architecture, and microenvironmental physical and metabolic features that define tumor niche prone to microinvasions. The identified physical properties of the matrix elucidate conditions that can facilitate or prevent the progression of such microinvasions. The presented method provides also a tool for quantifying morphological and immunohistochemical properties of individual cells within the mammary ducts and ductal microinvasion, as well as for testing biomechanical hypotheses of tumor cell-tumor matrix interactions. These findings can be compared to the patient histology samples and help define criteria for identification of changes in tumor architecture and future development of new diagnostic methods. Citation Format: Katarzyna A. Rejniak, Sharan Poonja, Shreya Mathur, Jessica Kingsley, Marilyn Bui. ECM mechanical and metabolic architecture during early ductal invasions: integrating in silico modeling, histology-based machine learning and mechanobiology [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr LT017.