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

cancer cancer biomarker cancer stem cell epithelial-to-mesenchyme-transition

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
22 Oct 2024
Historique:
received: 16 01 2024
revised: 25 07 2024
accepted: 27 09 2024
medline: 30 10 2024
pubmed: 30 10 2024
entrez: 29 10 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.cell.2024.09.046 PMID: 39471809
pubmed: 39471809
pii: S0092-8674(24)01146-2
doi: 10.1016/j.cell.2024.09.046
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

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.

Auteurs

Karolina Punovuori (K)

Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland.

Fabien 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.

Yekaterina A 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.

Mirjam I Binner (MI)

Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.

Satu-Marja Myllymäki (SM)

Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland.

Gautier Follain (G)

Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.

Kai Kruse (K)

Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.

Johannes Routila (J)

Department for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland.

Teemu Huusko (T)

Department for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland.

Teijo Pellinen (T)

Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.

Jaana 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.

Noemi Kedei (N)

Collaborative Protein Technology Resource, Office of Science and Technology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

Sami 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.

Antti 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.

Johanna 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.

Sara A 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.

Classifications MeSH