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Plate IV.83 · Publications

Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression

Article in Cancer Cell, August 2025.

Open accessmiRNA, Target, Cancer

  1. Lisa Schweizer
  2. Hilary A. Kenny
  3. Rahul Krishnan
  4. Lucy Kelliher
  5. Agnes J. Bilecz
  6. Janna Heide
  7. Leonhard Donle
  8. Aasa Shimizu
  9. Andreas Metousis
  10. Rachelle Mendoza
  11. Thierry M. Nordmann
  12. Sarah Rauch
  13. Sabrina Richter
  14. Yan Li
  15. Florian A. Rosenberger
  16. Maximilian T. Strauss
  17. Katherine C. Kurnit
  18. Marvin Thielert
  19. Edwin Rodriguez
  20. Johannes B. Müller-Reif
  21. S. Diane Yamada
  22. Fabian J. Theis
  23. Andreas Mund
  24. Ricardo R. Lastra
  25. Matthias Mann
  26. Ernst Lengyel

Abstract

Epithelial serous borderline tumors (SBT) are non-invasive neoplastic ovarian lesions that may recur as chemo-resistant low-grade serous cancer (LGSC). While genetic alterations suggest a common origin, the transition from SBT to LGSC remains poorly understood. Here, we integrate cell-type resolved spatial proteomics and transcriptomics to elucidate the evolution from SBT to LGSC and its corresponding metastases in both stroma and tumor. The transition occurs within the epithelial compartment through an intermediary stage with micropapillary features, during which LGSC overexpresses c-Met and several brain-specific proteins. Within the tumor microenvironment, interconnectivity between cancer and stromal cells, along with enzymes degrading a packed extracellular matrix, suggests functional collaboration among various cell types. We functionally validated 16 drug targets identified through integrated spatial transcriptomics and proteomics. Combined treatment targeting CDK4/6 (milciclib) and FOLR1 (mirvetuximab) achieved significant tumor reduction in vivo, representing a promising therapeutic strategy for LGSC.

Versions2

  1. PublishedCancer Cell10.1016/j.ccell.2025.06.004
  2. PreprintmedRxiv10.1101/2023.11.13.23298409

Cite

@article{schweizer2025spatial,
  title = {{Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression}},
  author = {Schweizer, Lisa and Kenny, Hilary A. and Krishnan, Rahul and Kelliher, Lucy and Bilecz, Agnes J. and Heide, Janna and Donle, Leonhard and Shimizu, Aasa and Metousis, Andreas and Mendoza, Rachelle and Nordmann, Thierry M. and Rauch, Sarah and Richter, Sabrina and Li, Yan and Rosenberger, Florian A. and Strauss, Maximilian T. and Kurnit, Katherine C. and Thielert, Marvin and Rodriguez, Edwin and Müller-Reif, Johannes B. and Yamada, S. Diane and Theis, Fabian J. and Mund, Andreas and Lastra, Ricardo R. and Mann, Matthias and Lengyel, Ernst},
  journal = {Cancer Cell},
  publisher = {Elsevier BV},
  year = {2025},
  month = aug,
  doi = {10.1016/j.ccell.2025.06.004},
  url = {https://doi.org/10.1016/j.ccell.2025.06.004},
  pmid = {40578359},
  pmcid = {PMC12233949}
}
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