Cancer develops within a heterogeneous ecosystem where malignant cells interact dynamically with vascular and immune components in a complex tumor-immune microenvironment (TIME). Elevated levels of extracellular matrix (ECM), along with physicochemical mediators such as fluid flow and mechanical forces, are hallmarks of the TIME. While genetic mutations initiate the transformation of normal cells into cancerous ones, growing evidence indicates that ECM composition and biophysical cues within the TIME play critical roles in regulating key tumor behaviors, including cell migration, invasion, angiogenesis, drug responses, and immune cell infiltration. The advent of microscale engineered models, integrating biological elements with quantitative engineering tools, offers unique platforms to recapitulate essential structural and functional features of the tumor microenvironment in vitro. These microengineered tissue models enable the generation of physicochemical cues, such as fluidic flow, to systematically investigate their roles in modulating vascular properties and immune responses during cancer progression. My research focuses on elucidating how ECM-derived physicochemical cues regulate angiogenesis and immune cell behavior in cancer using these microengineered tissue platforms. In this talk, I will first discuss how ECM composition and biophysical properties modulate angiogenic function in responses to fluid flow. Our findings show that hyaluronic acid enhances interstitial flow–mediated angiogenesis by increasing ECM stiffness and pore size. The second part of the talk will highlight our work on microglia activation and invasion in brain cancer, where we demonstrate that glioblastoma-induced microglia invasion is dependent on cellular contractility but independent of matrix degradation. I will also briefly present our recent efforts in engineering cancer spheroids to develop physiologically relevant tumor models. Lastly, I will share the vision for my independent research program, which aims to advance our understanding of how physicochemical regulators govern angiogenesis and immune responses in the context of cancer progression, inflammation, and brain immunology through integrative cancer bioengineering approaches.
