Systematic comparison of pancreatic ductal adenocarcinoma models identifies a conserved highly plastic basal cell state Journal Article
| Authors: | Pitter, K. L.; Grbovic-Huezo, O.; Joost, S.; Singhal, A.; Blum, M.; Wu, K.; Holm, M.; Ferrena, A.; Bhutkar, A.; Hudson, A.; Lecomte, N.; de Stanchina, E.; Chaligne, R.; Iacobuzio-Donahue, C. A.; Pe'er, D.; Tammela, T. |
| Article Title: | Systematic comparison of pancreatic ductal adenocarcinoma models identifies a conserved highly plastic basal cell state |
| Abstract: | Intratumoral heterogeneity and cellular plasticity have emerged as hallmarks of cancer, including pancreatic ductal adenocarcinoma (PDAC). As PDAC portends a dire prognosis, a better understanding of the mechanisms underpinning cellular diversity in PDAC is crucial. Here, we investigated the cellular heterogeneity of PDAC cancer cells across a range of in vitro and in vivo growth conditions using single-cell genomics. Heterogeneity contracted significantly in two-dimensional and three-dimensional cell culture models but was restored upon orthotopic transplantation. Orthotopic transplants reproducibly acquired cell states identified in autochthonous PDAC tumors, including a basal state exhibiting coexpression and coaccessibility of epithelial and mesenchymal genes. Lineage tracing combined with single-cell transcriptomics revealed that basal cells display high plasticity in situ. This work defines the impact of cellular growth conditions on phenotypic diversity and uncovers a highly plastic cell state with the capacity to facilitate state transitions and promote intratumoral heterogeneity in PDAC. SIGNIFICANCE: This work provides important insights into how different model systems of pancreatic ductal adenocarcinoma mold the phenotypic space of cancer cells, highlighting the power of in vivo models. ©2022 American Association for Cancer Research. |
| Keywords: | genetics; pancreatic neoplasms; carcinoma, pancreatic ductal; pathology; pancreas carcinoma; pancreas tumor; pancreatic ducts; plastic; plastics; humans; human; pancreatic duct |
| Journal Title: | Cancer Research |
| Volume: | 82 |
| Issue: | 19 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2022-10-01 |
| Start Page: | 3549 |
| End Page: | 3560 |
| Language: | English |
| DOI: | 10.1158/0008-5472.Can-22-1742 |
| PUBMED: | 35952360 |
| PROVIDER: | scopus |
| PMCID: | PMC9532381 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2022 -- Source: Scopus |
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