PuSH - Publikationsserver des Helmholtz Zentrums München

Schweizer, L.* ; Kenny, H.A.* ; Krishnan, R.* ; Kelliher, L.* ; Bilecz, A.J.* ; Heide, J.* ; Donle, L.* ; Shimizu, A.* ; Metousis, A.* ; Mendoza, R.* ; Nordmann, T.M.* ; Rauch, S.* ; Richter, S. ; Li, Y.* ; Rosenberger, F.A.* ; Strauss, M.T.* ; Kurnit, K.C.* ; Thielert, M.* ; Rodriguez, E.* ; Müller-Reif, J.B.* ; Yamada, S.D.* ; Theis, F.J. ; Mund, A.* ; Lastra, R.R.* ; Mann, M.* ; Lengyel, E.*

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

Cancer Cell, DOI: 10.1016/j.ccell.2025.06.004 (2025)
Postprint DOI PMC
Open Access Green
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.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Borderline Tumor ; Deep Visual Proteomics ; Low-grade Serous Cancer ; Mass Spectrometry ; Metastasis ; Ovarian Cancer ; Pathology ; Proteomics ; Transcriptomics
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Zeitschrift Cancer Cell
Verlag Cell Press
Verlagsort Cambridge, Mass.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)