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

J 2024

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

PROCHÁZKOVÁ, Jiřina; Radek FEDR; Barbora HRADILOVÁ; Barbora KVOKAČKOVÁ; Josef SLAVIK et al.

Základní údaje

Originální název

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

Autoři

Vydání

JOURNAL OF LIPID RESEARCH, AMSTERDAM, ELSEVIER, 2024, 0022-2275

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.100

Označené pro přenos do RIV

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

phenotypic plasticity; breast cancer glycosphingolipids; surface profiling; epithelial cells; stromal-like cells

Štítky

RIV ne

Změněno: 25. 12. 2025 18:10, Mgr. Jiřina Procházková, Ph.D.

Anotace

V originále

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

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

Citovat

PROCHÁZKOVÁ, Jiřina; Radek FEDR; Barbora HRADILOVÁ; Barbora KVOKAČKOVÁ; Josef SLAVIK; Ondrej KOVAC; Miroslav MACHALA; Pavel FABIAN; Jiri NAVRATIL; Simona KRACALIKOVA; Monika LEVKOVA; Petra OVESNÁ; Jan BOUCHAL a Karel SOUČEK. Single-cell profiling of surface glycosphingolipids opens a new dimension for deconvolution of breast cancer intratumoral heterogeneity and phenotypic plasticity. JOURNAL OF LIPID RESEARCH. AMSTERDAM: ELSEVIER, 2024, roč. 65, č. 9, s. 1-15. ISSN 0022-2275. Dostupné z: https://doi.org/10.1016/j.jlr.2024.100609.

@article{2542499,
   author = {Procházková, Jiřina and Fedr, Radek and Hradilová, Barbora and Kvokačková, Barbora and Slavik, Josef and Kovac, Ondrej and Machala, Miroslav and Fabian, Pavel and Navratil, Jiri and Kracalikova, Simona and Levkova, Monika and Ovesná, Petra and Bouchal, Jan and Souček, Karel},
   article_location = {AMSTERDAM},
   article_number = {9},
   doi = {https://doi.org/10.1016/j.jlr.2024.100609},
   keywords = {phenotypic plasticity; breast cancer glycosphingolipids; surface profiling; epithelial cells; stromal-like cells},
   language = {eng},
   issn = {0022-2275},
   journal = {JOURNAL OF LIPID RESEARCH},
   title = {Single-cell profiling of surface glycosphingolipids opens a new dimension for deconvolution of breast cancer intratumoral heterogeneity and phenotypic plasticity},
   url = {https://www.sciencedirect.com/science/article/pii/S0022227524001147?via%3Dihub},
   volume = {65},
   year = {2024}
}

TY  - JOUR
ID  - 2542499
AU  - Procházková, Jiřina - 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
PY  - 2024
TI  - Single-cell profiling of surface glycosphingolipids opens a new dimension for deconvolution of breast cancer intratumoral heterogeneity and phenotypic plasticity
JF  - JOURNAL OF LIPID RESEARCH
VL  - 65
IS  - 9
SP  - 1-15
EP  - 1-15
PB  - ELSEVIER
SN  - 00222275
KW  - phenotypic plasticity
KW  - breast cancer glycosphingolipids
KW  - surface profiling
KW  - epithelial cells
KW  - stromal-like cells
UR  - https://www.sciencedirect.com/science/article/pii/S0022227524001147?via%3Dihub
N2  - 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
ER  -

PROCHÁZKOVÁ, Jiřina; Radek FEDR; Barbora HRADILOVÁ; Barbora KVOKAČKOVÁ; Josef SLAVIK; Ondrej KOVAC; Miroslav MACHALA; Pavel FABIAN; Jiri NAVRATIL; Simona KRACALIKOVA; Monika LEVKOVA; Petra OVESNÁ; Jan BOUCHAL a Karel SOUČEK. Single-cell profiling of surface glycosphingolipids opens a new dimension for deconvolution of breast cancer intratumoral heterogeneity and phenotypic plasticity. \textit{JOURNAL OF LIPID RESEARCH}. AMSTERDAM: ELSEVIER, 2024, roč.~65, č.~9, s.~1-15. ISSN~0022-2275. Dostupné z: https://doi.org/10.1016/j.jlr.2024.100609.

Přehled o publikaci