Tumors invade surrounding tissue as cancer progresses, but the heterogeneity of cell types at the tumor-stroma interface and the complexity of their interactions has hampered mechanistic insight required for efficient therapeutic targeting. In this webinar, I will discuss a recently published study whereby combining single-cell and spatial transcriptomic data taken from human basal cell carcinomas, we defined the cellular contributors to tumor progression. In the invasive niche, tumor cells exhibit a collective migration phenotype, characterized by the expression of cell-cell junction complexes. In close proximity, we identified cancer-associated fibroblasts with extracellular matrix-remodeling features. Tumor cells strongly express the cytokine Activin A, and an increased Activin A-induced gene signature was found in adjacent cancer-associated fibroblast subpopulations. Altogether, our data identifies cell populations and their transcriptional reprogramming that contribute to the spatial organization of the invasive niche of basal cell carcinoma. In this study, we have demonstrated the power of integrated spatial and single-cell multi-omics to decipher the properties of invasive niches in cancer and develop targeted therapies.
Yerly L et al, Nat Commun (2022)
Learning Objectives:
1. Describe the characteristics of invasive niches of basal cell carcinoma in terms of cell types and gene expression profiles.
2. Explain how spatial transcriptomics can be used in conjunction with single cell analysis to better understand tissue heterogeneity at the tumor-stroma interface.
3. Discuss how the cytokine Activin A affects the behavior and activity of cancer-associated fibroblasts.