Dissecting the Role of Heterogeneity in Squamous Skin Cancer Metastasis by Daphne Superville

Daphne Superville

UC San Francisco | Merrill Randol

Metastasis, the process by which tumor cells spread to distant organs, remains an untreatable facet of tumor progression and is responsible for the majority of cancer-related deaths. The heterogeneity of tumors further complicates treatment of advanced disease; apart from being associated with worse prognosis, it has also been shown that multiple subpopulations of cells within a tumor can go on to seed metastases. This work aims to understand how these subpopulations interact to facilitate metastasis and tumor progression.


In the era of personalized medicine, the near ubiquity of intratumoral heterogeneity (ITH) across different cancers has emerged as one of the most prominent obstacles for targeted therapies. Most tumors begin from a single mutant cell, over time acquiring additional mutations to create a heterogeneous tumor composed of distinct subpopulations of cells (“subclones”). Tumors with high ITH are associated with a worse prognosis and increased malignancy. Metastasis is an extremely selective, multistep process whereby tumor cells disseminate to distant organs. Several studies have observed that multiple tumor subpopulations can seed metastases, leading us to investigate whether metastasis is driven by synergistic behaviors between tumor cells. Using a fluorescent reporter-based lineage tracing mouse model, we can isolate subpopulations of cells within malignant squamous skin tumors to effectively deconstruct ITH. In preliminary studies involving a polyclonal lymph node metastasis cell line we found that subpopulations can have different metastatic abilities and immune infiltrates when grown independently or together in vivo. These studies will shed light on how heterogeneous tumors progress through the interactions of their constituent subpopulations.


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