Soft Matter Seminar: “Tumor Microenvironment Interactions Driving Cancer Progression”

The Syracuse University Department of Physics Soft Matter Group is pleased to welcome Michelle Dawson, Associate Professor of Molecular Biology, Cell Biology and Biochemistry, Brown University for her talk titled, “Tumor Microenvironment Interactions Driving Cancer Progression.”

Intratumor heterogeneity represents a major challenge in understanding and treating cancer. This includes intrinsic differences in cancer cells and morphological differences in tumor architectures. My research applies single-cell biophysical analysis and novel tumor microenvironment models to investigate links between altered or invasive cell populations and disease progression. My work shows how the evolution of invasive cell populations can protect, foster, and even prime tumor cells against exogenous stress. This talk will highlight my recent work on therapy induced senescence (TIS) and polyploid giant cancer cells (PGCCs) – resilient subpopulations contributing to chemoresistance and disease recurrence. Since growth is arrested in TIS, this has been considered a positive treatment outcome; however, senescent cells remain metabolically active and develop a senescence associated secretory phenotype (SASP), which can promote cancer progression. In addition, a small number of cancer cells are able to escape this dormant state to contribute to tumor recurrence and resistance. PGCCs are a novel and understudied subpopulation of dormant and multinucleated giant cancer cells that exhibit multiple features of TIS. Although PGCCs share many characteristics with senescent cells, including their large size, arrested cell cycle, and SASP, they also differ from senescent cells, in their ability to escape TIS by undergoing amitotic budding to form new tumors. Increased numbers of large PGCCs are seen in late stage and metastatic cancers; yet there is a significant gap in our understanding of what allows PGCCs to survive chemotherapy and undergo budding to form chemo resistant and mitotic cancer cells. Through single cell, multicellular, and tissue level studies, we investigated how their cytoskeletal alterations, dysregulated metabolism, and inflammatory SASP contribute to PGCC survival during treatment. Our data suggests that their unique biophysical properties are linked to their dysregulated metabolism and altered cell structure. This presentation will focus on our recent work investigating the role of TIS on cancer and stromal cell interactions in the tumor. These studies provide critical information about how aging and TIS affect tumor microenvironments.