bridging the gap between
mechanistic and the clinic
Understanding how living cells migrate in reliable and orchestrated ways is essential to understanding the most fundamental functions of life. Cell migration is a complex behavior that emerges from the interactions of tens of thousands of molecular parts. Still, much of what is known is limited to the context of cell migration on artificial 2D environments. Through the development of quantitative microscopy and imaging techniques, three-dimensional matrix engineering, and molecular engineering, the Fraley Lab is advancing migration research into the third dimension.
From the benchtop...
Understanding induction and regulation of metastatic migration
By developing a novel 3D collagen matrix engineering technique, we have discovered that specific matrix architectures force cancer cells to alter their gene expression and migration behavior. The result is a switch from individual to collective migration and the development of network-like structures. This aggressive cancer cell phenotype, known as vasculogenic mimicry, has been observed in clinical biopsies in over 16 tumor types and is associated with metastatic progression. The novel gene signature we discovered predicts metastasis in clinical data across nine human tumor types. We are working to identify potential therapeutic strategies by studying how cancer cells use these genes to mimic vasculature and spread into the bloodstream.
We are working to develop a mouse model of collagen-induced vasculogenic mimicry. This will allow functional gene studies and potential therapeutic targets to be validated. These studies are also necessary to gain a clearer understanding of how vasculogenic mimicry contributes to circulating tumor cells and metastasis.
Mechanics of migration
Since all eukaryotic cells share the same fundamental motility machinery, how do different cell types tune their machinery to achieve different migration behaviors? How does a 3D environment direct cell migration behavior differently than a 2D environment? We are developing a new microscopy platform and statistical models of cell migration machinery that will enable us to answer these questions.
Dr. Fraley's talk on cancer cell migration at the 2022 Cancer Systems Biology Conference.
To the bedside...
Pathways that modulate cancer stem cell aggression and metastatic potential are being tested for conservation across mouse models and human tissue samples. Histopathological analyses will serve to validate our mouse model for further mechanistic and therapeutic studies.