Spatial biology: the new frontier in breast cancer research and 3D models

Breast cancer patients nowadays continue facing unmet clinical needs, caused by the broad mutational landscape expressed by different breast cancer subtypes, determining a more localized, invasive, or metastatic phenotype. [1] The bone tissue is a well-known site for breast cancer metastasis, though the initiating mechanisms are not entirely understood. [2] In recent years, the fields of 3D models bioengineering, -omics, and spatial biology have been advancing rapidly. With their combination, the intent is to recreate a tumor model with defined tumor microenvironment and architecture, that can be biologically validated with high-throughput, spatially resolved techniques, to matched findings observed in patients. [3]

In this work we hypothesized that differences in the bone tissue niche, specifically in the calcium content, could influence the metastatic seeding of breast cancer cells. We initially observed a differential motility and migration response when MDA-MB-231 breast cancer cells were encapsulated in silk fibroin hydrogels containing different amounts of calcium. Moreover, breast cancer cells exhibited dual behavior in either enriched or lower calcium settings, when also the bone niche cellular compartment (namely osteoblasts and bone marrow stem cells) were present. This highlights the crucial need to further integrate cutting-edge -omics and spatial biology techniques to fully understand cells interaction and behavior. As initial model validation, we were interested to check if breast cancer patients harbor alterations in calcium-regulated pathways. We analyzed publicly available -omics datasets using the bioinformatic tool cBioportal, integrating information with Gene Ontology and KEGG tools. Initial findings showed alterations in a 20-genes set list, particularly in the breast cancer patients cohorts that included invasive and metastatic subtypes. Overall, these preliminary results show a promising mechanism to unravel the basis of the breast-to-bone metastatic process. With the integration of spatial -omics analysis, this system has the potential to be used for novel biomarkers and therapeutic targets discovery for patients.