{"id":888,"date":"2024-09-07T07:28:30","date_gmt":"2024-09-07T05:28:30","guid":{"rendered":"https:\/\/lc.ibp.cz\/?p=888"},"modified":"2024-09-09T09:36:54","modified_gmt":"2024-09-09T07:36:54","slug":"single-cell-profiling-of-surface-glycosphingolipids-opens-a-new-dimension-for-deconvolution-of-breast-cancer-intratumoral-heterogeneity-and-phenotypic-plasticity","status":"publish","type":"post","link":"https:\/\/lc.ibp.cz\/?p=888","title":{"rendered":"Single-cell profiling of surface glycosphingolipids opens a new dimension for deconvolution of breast cancer intratumoral heterogeneity and phenotypic plasticity"},"content":{"rendered":"\n

Ji\u0159ina Proch\u00e1zkov\u00e1<\/a>\u00a0<\/sup>,\u00a0Radek Fedr<\/a>\u00a0<\/sup>,\u00a0Barbora Hradilov\u00e1<\/a>\u00a0<\/sup>,\u00a0Barbora Kvoka\u010dkov\u00e1<\/a>\u00a0<\/sup>,\u00a0Josef Slav\u00edk<\/a>\u00a0<\/sup>,\u00a0Ondrej Kov\u00e1\u010d<\/a>\u00a0<\/sup>,\u00a0Miroslav Machala<\/a>\u00a0<\/sup>,\u00a0Pavel Fabian<\/a>\u00a0<\/sup>,\u00a0Ji\u0159\u00ed Navr\u00e1til<\/a>\u00a0<\/sup>,\u00a0Simona Kr\u00e1\u010dal\u00edkov\u00e1<\/a>\u00a0<\/sup>,\u00a0Monika Levkov\u00e1<\/a>\u00a0<\/sup>,\u00a0Petra Ovesn\u00e1<\/a>\u00a0<\/sup>,\u00a0Jan Bouchal<\/a>\u00a0<\/sup>,\u00a0Karel Sou\u010dek<\/a><\/p>\n\n\n\n

J Lipid Res, 2024 Jul 30;65(9):100609.\u00a0DOI:\u00a010.1016\/j.jlr.2024.100609<\/a><\/p>\n\n\n\n

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 single-cell approach offers promising avenues for further exploration.<\/p>\n\n\n\n

Keywords:\u00a0<\/strong>breast cancer; epithelial cells; glycosphingolipids; phenotypic plasticity; stromal-like cells; surface profiling.<\/p>\n\n\n\n

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<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Ji\u0159ina Proch\u00e1zkov\u00e1\u00a0,\u00a0Radek Fedr\u00a0,\u00a0Barbora Hradilov\u00e1\u00a0,\u00a0Barbora Kvoka\u010dkov\u00e1\u00a0,\u00a0Josef Slav\u00edk\u00a0,\u00a0Ondrej Kov\u00e1\u010d\u00a0,\u00a0Miroslav Machala\u00a0,\u00a0Pavel Fabian\u00a0,\u00a0Ji\u0159\u00ed Navr\u00e1til\u00a0,\u00a0Simona Kr\u00e1\u010dal\u00edkov\u00e1\u00a0,\u00a0Monika Levkov\u00e1\u00a0,\u00a0Petra Ovesn\u00e1\u00a0,\u00a0Jan Bouchal\u00a0,\u00a0Karel Sou\u010dek J Lipid Res, 2024 Jul 30;65(9):100609.\u00a0DOI:\u00a010.1016\/j.jlr.2024.100609 Glycosylated sphingolipids (GSLs) are a diverse group of cellular lipids typically reported as being rare in normal mammary tissue. … <\/p>\n","protected":false},"author":2,"featured_media":889,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[28],"tags":[],"class_list":["post-888","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publication"],"_links":{"self":[{"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=\/wp\/v2\/posts\/888"}],"collection":[{"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=888"}],"version-history":[{"count":1,"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=\/wp\/v2\/posts\/888\/revisions"}],"predecessor-version":[{"id":890,"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=\/wp\/v2\/posts\/888\/revisions\/890"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=\/wp\/v2\/media\/889"}],"wp:attachment":[{"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=888"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=888"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lc.ibp.cz\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=888"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}