About This Project

Cancer spread begins when invasive cells cross the basement membrane, but current models fail to capture this step. To overcome this, we will engineer a basement membrane using Human Umbilical Cord-derived Mesenchymal Stem Cells (UC-MSCs) over a collagen matrix and quantify invasion. We hypothesize that Myh9, a protein that generates cellular mechanical forces, promotes cancer cell invasion across the basement membrane. This model can also be used to study other regulators of invasion.

Ask the Scientists

What is the context of this research?

Cancer invasion depends not only on signaling but also on the ability of tumor cells to generate mechanical forces to cross tissue barriers. A key early barrier is the basement membrane, a specialized extracellular matrix, which is remodeled and breached during metastasis. Most in vitro invasion models use simplified matrices that fail to reproduce its structure and mechanics, limiting understanding of force-driven invasion.

Stromal cell–derived matrices better mimic native tissue by recreating key structural and mechanical features of the extracellular environment. These systems reflect stromal remodeling forces present in tumors, where contractile cells actively reshape the microenvironment.

Myh9 (non-muscle myosin IIA) regulates cell-contracting forces and has been linked to tumor cell invasion. We hypothesize that Myh9-driven mechanical forces promote cancer cell invasion across this physiologically assembled basement membrane.

What is the significance of this project?

Understanding how tumor cells cross the basement membrane is critical for identifying mechanisms that drive early invasion and metastasis. This is especially important as 90% of cancer patients die from metastasis, not the original tumor. While many studies have focused on biochemical signaling pathways that regulate cell behavior, less is known about how force-generating machinery within cells contributes to overcoming tissue barriers.

Myh9 is a key protein in the invasion system and plays an important role in cellular force generation and mechanical behavior. By determining how Myh9 perturbation affects tumor cell crossing of a self-assembled basement membrane interface, this project will provide insight into mechanisms underlying mechanically driven invasion.

This work also establishes a more physiologically relevant invasion system that better reflects basement membrane organization and tissue architecture in the body, improving the biological studies of cancer invasion.

What are the goals of the project?

Our goals are to generate a basement membrane–like layer by culturing UC-MSCs under defined conditions that promote self-organization. Formation and structural integrity of this layer will be confirmed using immunofluorescence imaging of basement membrane proteins. A layered model will then be constructed by placing a stromal matrix beneath the engineered basement membrane. Within this system, we will examine how changes in Myh9 expression affect tumor cell movement through the basement membrane and into the underlying collagen matrix. Invasion will be quantified by assessing whether cells successfully cross the basement membrane and the extent to which they invade into the stromal matrix below.