July, 2024
July 2024
Maria Alcolea: Determinants of survival of early tumours
Jul 11, 2024, 12:52

Maria Alcolea: Determinants of survival of early tumours

Maria Alcolea, Group Leader at the Cambridge Stem Cell Institute, made the following post on X:

Did you know that not all newly forming tumours persist long-term? If you are intrigued to know what determines the survival of early tumours, check out our latest preprint! Work led by Greta Skrupskelyte and J. E. Rojo Arias.

We investigate what sets apart the tumours that remain long-term in the tissue from those that are eliminated. A crucial question to understand the early events in tumorigenesis, with implications for developing new preventive and therapeutic strategies.

We combine single-cell RNA sequencing and cell communication analysis, with lineage tracing, 3D heterotypic cultures, as well as in vivo grafting assays to identify the unique features of the few nascent tumours that avoid elimination, and survive long-term.

We demonstrate that surviving tumours are characterised by a stress-related epithelial state (marked by high SOX9 expression) that promotes mesenchymal mobilization and ECM remodelling via EFG signalling.

This leads to the formation of a fibrotic pre-cancer tumour niche that, in turn, feeds back on the epithelium promoting the growth and long-term survival of nascent tumours.

Remarkably, heterotypic in vitro and in vivo experiments, combining healthy epithelium and tumour stroma, demonstrate that the pre-cancerous niche alone is sufficient to confer tumour properties to epithelial cells. Perpetuating the tumour phenotype beyond genetic alterations.

Blocking epithelial-mesenchymal communication by either knocking-down SOX9 expression in the epithelium, or blocking fibronectin fibrillogenesis, which interferes with ECM assembly, hinders tumour survival and significantly reduces the tumour burden.

Big thanks to all authors: Yiteng Dang, Seungmin Han, Maria Teresa Bejar, Bartomeu Colom, JC Fowler, and Phil Jones, Wellcome Sanger Institute. Special thanks to the Rulands Group, Ludwig Maximilian University of Munich and Ben Simons, Gurdon Institute. We also extend our gratitude to the major funders: Wellcome Trust, Royal Society, The Medical Research Council, Worldwide Cancer Research, and Guts UK Charity.

Source: Maria Alcolea/X