Single-cell profiling of surface glycosphingolipids opens a new dimension for deconvolution of breast cancer intratumoral heterogeneity and phenotypic plasticity

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Publikace nespadá pod Fakultu sportovních studií, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
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PROCHAZKOVA Jirina FEDR Radek HRADILOVÁ Barbora KVOKAČKOVÁ Barbora SLAVIK Josef KOVAC Ondrej MACHALA Miroslav FABIAN Pavel NAVRATIL Jiri KRACALIKOVA Simona LEVKOVA Monika OVESNÁ Petra BOUCHAL Jan SOUČEK Karel

Rok publikování 2024
Druh Článek v odborném periodiku
Časopis / Zdroj JOURNAL OF LIPID RESEARCH
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://www.sciencedirect.com/science/article/pii/S0022227524001147?via%3Dihub
Doi http://dx.doi.org/10.1016/j.jlr.2024.100609
Klíčová slova phenotypic plasticity; breast cancer glycosphingolipids; surface profiling; epithelial cells; stromal-like cells
Přiložené soubory
Popis Glycosylated sphingolipids (GSLs) are a diverse group of cellular lipids typically reported as being rare in normal mammary tissue. In breast cancer (BCa), GSLs have emerged as noteworthy markers associated with breast cancer stem cells, mediators of phenotypic plasticity, and contributors to cancer cell chemoresistance. GSLs are potential surface markers that can uniquely characterize the heterogeneity of the tumor microenvironment, including cancer cell subpopulations and epithelial-mesenchymal plasticity (EMP). In this study, mass spectrometry analyses of the total sphingolipidome in breast epithelial cells and their mesenchymal counterparts revealed increased levels of Gb3 in epithelial cells and significantly elevated GD2 levels in the mesenchymal phenotype. To elucidate if GSL-related epitopes on BCa cell surfaces reflect EMP and cancer status, we developed and rigorously validated a 12-color spectral flow cytometry panel. This panel enables the simultaneous detection of native GSL epitopes (Gb3, SSEA1, SSEA3, SSEA4, and GD2), epithelial-mesenchymal transition markers (EpCAM, TROP2, and CD9), and lineage markers (CD45, CD31, and CD90) at the single-cell level. Next, the established panel was used for the analysis of BCa primary tumors and revealed surface heterogeneity in SSEA1, SSEA3, SSEA4, GD2, and Gb3, indicative of native epitope presence also on non-tumor cells. These findings further highlighted the phenotype- dependent alterations in GSL surface profiles, with differences between epithelial and stromal cells in the tumor. This study provides novel insights into BCa heterogeneity, shedding light on the potential of native GSL-related epitopes as markers for EMP and cancer status in fresh clinical samples. The developed
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