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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 43, 1495-1511.e7 (2025)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Borderline Tumor ; Deep Visual Proteomics ; Low-grade Serous Cancer ; Mass Spectrometry ; Metastasis ; Ovarian Cancer ; Pathology ; Proteomics ; Transcriptomics; Low-grade; Mirvetuximab Soravtansine; Cancer; Mutations; Pathway; Differentiation; Metastasis; Carcinomas; Cleavage; Origin
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Journal Cancer Cell
Quellenangaben Volume: 43, Issue: 8, Pages: 1495-1511.e7 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants Helmholtz Association
European Union Horizon
Swiss National Science Foundation (SNSF)
EMBO
International Max Planck Research School for Life Sciences-IMPRS-LS
Max Planck Society for Advancement of Science
Cellular Screening Center and Human Tissue Resource Center Cores at the University of Chicago - Cancer Center Support Grant
NIH/NCI