![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Preprint)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
7MB |
![[thumbnail of Supplementary Material]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Material)
1MB |
| Item Type: | Preprint |
|---|---|
| Title: | Spatiotemporal dynamics of tumor microenvironment remodeling |
| Creators: |
Lisek, Kamil  ORCID: https://orcid.org/0000-0002-2406-8830, Theurillat, Ilan ORCID: https://orcid.org/0000-0002-1125-1951, Pentimalli, Tancredi Massimo ORCID: https://orcid.org/0000-0002-8461-7918, Beier, Svea ORCID: https://orcid.org/0009-0006-6473-8487, León-Periñán, Daniel ORCID: https://orcid.org/0000-0002-7970-0362, Antonatou, Anna, Dubnov, Serafima, Müller, Marion, Hubl, Florian, Xhuri, Artemis, Romanowicz, Hanna, Smolarz, Beata, Montaudon, Elodie, Raimundo, Sandra ORCID: https://orcid.org/0009-0000-3353-5456, Margineanu, Anca ORCID: https://orcid.org/0000-0002-6634-9729, Schott, Marie ORCID: https://orcid.org/0009-0000-7393-2421, Kunz, Séverine ORCID: https://orcid.org/0000-0002-0131-3506, Marangoni, Elisabetta, Karaiskos, Nikos ORCID: https://orcid.org/0000-0001-7771-3947, Nitzan, Mor, Birchmeier, Walter ORCID: https://orcid.org/0000-0003-1173-0829 and Rajewsky, Nikolaus ORCID: https://orcid.org/0000-0002-4785-4332
|
| Abstract: | During tumorigenesis, interactions between tumor and stromal cells progressively remodel the tumor microenvironment (TME) towards pro-tumoral functions. Understanding early TME remodeling dynamics is therefore crucial for developing interceptive therapies. However, clinical samples typically provide isolated, late tumorigenesis snapshots. To overcome this limitation, we generated triple-negative breast cancer mice that develop multifocal, asynchronous tumors along a continuous luminal-to-basal transdifferentiation trajectory. Ordering spatial transcriptomes from 100+ ducts along this trajectory reveals the spatiotemporal dynamics of TME remodeling and underlying molecular mechanisms. Cancer-associated myofibroblasts (myCAFs) emerge as key players in advanced tumors, where they orchestrate pro-invasive remodeling of the tumor-stromal interface. myCAFs are conserved in patient-derived xenograft models and steer tumor trajectories towards invasive phenotypes when co-injected with tumor cells in syngeneic mice. Our study shows that temporal ordering of spatially-resolved disease snapshots unravels some of the molecular “forces” that, starting from the cell-of-origin, propel cells/microenvironments along a disease trajectory. |
| Keywords: | Animals, Mice |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2025.07.15.662972 |
| Date: | 18 July 2025 |
| Official Publication: | https://doi.org/10.1101/2025.07.15.662972 |
| Related to: |
Repository Staff Only: item control page
