Developing a Spatial Omics Atlas of Pancreatic Cancer
The Bailey laboratory is using spatial omics technologies to build a high-resolution atlas of pancreatic cancer, conceptualizing the tumor as a pathological organ. These methods integrate molecular profiling with spatial tissue context, allowing for the analysis of gene expression, protein interactions, and metabolic states within their original architectural framework.
This program aims to create a comprehensive spatial atlas that maps the tumor ecosystem not just as a collection of cells, but as an integrated system with distinct functional territories.This allows for the identification of spatial "ecotypes" or neighborhoods—such as fibrotic, metabolic, and immunosuppressive zones—that function like specialized tissues within the tumor organ. A critical application of this atlas is to understand inter-organ communication. This includes mapping how cancer cells adapt to new organ environments during metastasis and, crucially, dissecting the complex crosstalk within the primary tumor that facilitates this spread.
A key feature of this "tumor organ"; is its ability to develop its own infrastructure through processes like angiogenesis (the formation of new blood vessels) and neoneurogenesis (the recruitment and growth of new nerve fibers). Pancreatic cancer is characterized by a high incidence of perineural invasion (PNI), where cancer cells infiltrate nerve sheaths, a process strongly associated with local recurrence, pain, and poor prognosis. These neurovascular systems are not independent; there is significant crosstalk, with nerve-derived signals modulating angiogenesis and both structures serving as conduits for tumor progression. Spatial technologies are essential for decoding this neurovascular interplay. Spatial transcriptomics allows for the analysis of gene expression profiles directly at the interface of invaded nerves and cancer cells, revealing key signaling pathways involved in PNI, such as axon guidance and endocannabinoid metabolism. Furthermore, high-plex protein imaging platforms like Imaging Mass Cytometry (IMC) enable the simultaneous visualization of nerve fibers, endothelial cells, tumor cells, and various immune populations within a single tissue section. 53 This allows for the precise mapping of distinct "vascular niches"; and the characterization of the cells that support them. By understanding these spatial dynamics, the laboratory aims to identify novel biomarkers and therapeutic targets to disrupt the supportive neurovascular network of
