Multiparameter imaging reveals clinically relevant cancer cell-stroma interaction dynamics in head and neck cancer.

Autor:	Punovuori K; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Bertillot F; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany., Miroshnikova YA; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Binner MI; Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany., Myllymäki SM; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland., Follain G; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland., Kruse K; Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany., Routila J; Department for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland., Huusko T; Department for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland., Pellinen T; Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Hagström J; Department of Oral Pathology and Radiology, University of Turku, Turku University Hospital, Turku, Finland; Research Programs Unit, Translational Cancer Medicine, University of Helsinki, Helsinki, Finland; Department of Pathology, University of Helsinki, 00014 Helsinki, Finland., Kedei N; Collaborative Protein Technology Resource, Office of Science and Technology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Ventelä S; Department for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland., Mäkitie A; Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland; Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, HUS, 00029 Helsinki, Finland; Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institute and Karolinska University Hospital, 17176 Stockholm, Sweden., Ivaska J; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland; Foundation for the Finnish Cancer Institute, Tukholmankatu 8, 00014 Helsinki, Finland., Wickström SA; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany; Helsinki Institute of Life Science, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland; Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland. Electronic address: sara.wickstrom@mpi-muenster.mpg.de.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Dec 12; Vol. 187 (25), pp. 7267-7284.e20. Date of Electronic Publication: 2024 Oct 28.
DOI:	10.1016/j.cell.2024.09.046
Abstrakt:	Epithelial tumors are characterized by abundant inter- and intra-tumor heterogeneity, which complicates diagnostics and treatment. The contribution of cancer-stroma interactions to this heterogeneity is poorly understood. Here, we report a paradigm to quantify phenotypic diversity in head and neck squamous cell carcinoma (HNSCC) with single-cell resolution. By combining cell-state markers with morphological features, we identify phenotypic signatures that correlate with clinical features, including metastasis and recurrence. Integration of tumor and stromal signatures reveals that partial epithelial-mesenchymal transition (pEMT) renders disease outcome highly sensitive to stromal composition, generating a strong prognostic and predictive signature. Spatial transcriptomics and subsequent analyses of cancer spheroid dynamics identify the cancer-associated fibroblast-pEMT axis as a nexus for intercompartmental signaling that reprograms pEMT cells into an invasive phenotype. Taken together, we establish a paradigm to identify clinically relevant tumor phenotypes and discover a cell-state-dependent interplay between stromal and epithelial compartments that drives cancer aggression. Competing Interests: Declaration of interests K.P., F.B., Y.A.M., and S.A.W. are listed as inventors on a patent application related to this work, filed through the technology transfer office of the University of Helsinki, with UoH being the patent applicant. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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