Pancreatic Cancer Metastases Harbor Evidence of Polyclonality
Menée à l'aide d'un modèle murin de cancer du pancréas, cette étude met en évidence la dynamique cellulaire de l'évolution tumorale et le rôle joué par l'hétérogénéité clonale dans le processus métastatique
Studies of the cancer genome have demonstrated that tumors are comprised of multiple sub-clones with varied genetic and phenotypic properties. However, little is known about how metastases arise and evolve from these sub-clones. To understand the cellular dynamics that drive metastasis, we used multi-color lineage tracing technology in an autochthonous mouse model of pancreatic cancer. Here, we report that precursor lesions exhibit significant clonal heterogeneity but that this diversity decreases during pre-malignant progression. Furthermore, we present evidence that a significant fraction of metastases are polyclonally seeded by distinct tumor sub-clones. Finally, we show that clonality during metastatic growth - leading to either monoclonal or polyclonal expansion - differs based on the site of metastatic invasion. These results provide an unprecedented window into the cellular dynamics of tumor evolution and suggest that heterotypic interactions between tumor subpopulations contribute to metastatic progression in native tumors.