Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry

• Published in: Nature methods Vol. 11; no. 4; pp. 417 - 422
• Main Authors: Giesen, Charlotte, Wang, Hao A O, Schapiro, Denis, Zivanovic, Nevena, Jacobs, Andrea, Hattendorf, Bodo, Schüffler, Peter J, Grolimund, Daniel, Buhmann, Joachim M, Brandt, Simone, Varga, Zsuzsanna, Wild, Peter J, Günther, Detlef, Bodenmiller, Bernd
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-04-2014; Nature Publishing Group
• Subjects: 13; 13/31; 13/51; 14; 14/1; 14/63; 631/553; 631/61; 96; 96/95; Bioinformatics; Biological Microscopy; Biological Techniques; Biomedical Engineering/Biotechnology; Breast Neoplasms - metabolism; Cell Line; Cellular biology; Cytochemistry; Cytogenetics; Development and progression; Epithelial Cells - cytology; Epithelial Cells - metabolism; Female; Gene Expression Regulation, Neoplastic - physiology; Genetic aspects; Heterogeneity; Humans; Image Cytometry - methods; Life Sciences; Metals; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Proteins; Proteomics; Subpopulations; Tissues; Tumors; United States
• ISSN: 1548-7091; 1548-7105
• DOI: 10.1038/nmeth.2869

This paper reports the use of mass cytometry on adherent cells and tissue samples for highly multiplexed imaging at subcellular resolution.
Mass cytometry enables high-dimensional, single-cell analysis of cell type and state. In mass cytometry, rare earth metals are used as reporters on antibodies. Analysis of metal abundances using the mass cytometer allows determination of marker expression in individual cells. Mass cytometry has previously been applied only to cell suspensions. To gain spatial information, we have coupled immunohistochemical and immunocytochemical methods with high-resolution laser ablation to CyTOF mass cytometry. This approach enables the simultaneous imaging of 32 proteins and protein modifications at subcellular resolution; with the availability of additional isotopes, measurement of over 100 markers will be possible. We applied imaging mass cytometry to human breast cancer samples, allowing delineation of cell subpopulations and cell-cell interactions and highlighting tumor heterogeneity. Imaging mass cytometry complements existing imaging approaches. It will enable basic studies of tissue heterogeneity and function and support the transition of medicine toward individualized molecularly targeted diagnosis and therapies.