Figure 4 from Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node Stroma
<p>Deregulated metabolism in response to tumor factors and LA. <b>A,</b> Using the RNA-seq data from <a href="#fig3" target="_blank">Fig. 3</a>, depicted here are the top 10 most significant GO terms for ”biological process” using all significantly u...
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| author | Angela Riedel (15130557) |
| author2 | Moutaz Helal (15130560) Luisa Pedro (15130563) Jonathan J. Swietlik (15130566) David Shorthouse (2733004) Werner Schmitz (15130569) Lisa Haas (15130572) Timothy Young (15130575) Ana S.H. da Costa (15130578) Sarah Davidson (8254992) Pranjali Bhandare (13789834) Elmar Wolf (14952454) Benjamin A. Hall (199856) Christian Frezza (15130581) Thordur Oskarsson (2313193) Jacqueline D. Shields (14889899) |
| author2_role | author author author author author author author author author author author author author author author |
| author_facet | Angela Riedel (15130557) Moutaz Helal (15130560) Luisa Pedro (15130563) Jonathan J. Swietlik (15130566) David Shorthouse (2733004) Werner Schmitz (15130569) Lisa Haas (15130572) Timothy Young (15130575) Ana S.H. da Costa (15130578) Sarah Davidson (8254992) Pranjali Bhandare (13789834) Elmar Wolf (14952454) Benjamin A. Hall (199856) Christian Frezza (15130581) Thordur Oskarsson (2313193) Jacqueline D. Shields (14889899) |
| author_role | author |
| dc.creator.none.fl_str_mv | Angela Riedel (15130557) Moutaz Helal (15130560) Luisa Pedro (15130563) Jonathan J. Swietlik (15130566) David Shorthouse (2733004) Werner Schmitz (15130569) Lisa Haas (15130572) Timothy Young (15130575) Ana S.H. da Costa (15130578) Sarah Davidson (8254992) Pranjali Bhandare (13789834) Elmar Wolf (14952454) Benjamin A. Hall (199856) Christian Frezza (15130581) Thordur Oskarsson (2313193) Jacqueline D. Shields (14889899) |
| dc.date.none.fl_str_mv | 2025-11-25T13:44:07Z |
| dc.identifier.none.fl_str_mv | 10.1158/2326-6066.30710353 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/Figure_4_from_Tumor-Derived_Lactic_Acid_Modulates_Activation_and_Metabolic_Status_of_Draining_Lymph_Node_Stroma/30710353 |
| dc.rights.none.fl_str_mv | CC BY info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Cancer Tumor Biology Molecular and Cellular Biology Immuno-oncology Immunology Immune responses to cancer Metabolism Mitochondrial function Progression, Invasion & Metastasis Metastasis Tumor Microenvironment Tumor-stromal cell interactions |
| dc.title.none.fl_str_mv | Figure 4 from Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node Stroma |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | <p>Deregulated metabolism in response to tumor factors and LA. <b>A,</b> Using the RNA-seq data from <a href="#fig3" target="_blank">Fig. 3</a>, depicted here are the top 10 most significant GO terms for ”biological process” using all significantly upregulated genes in <i>in vitro</i> cultured FRCs treated for 4 days with B16.F10 TCM versus CCM. <b>B,</b> Heatmap displaying significant deregulated genes in TCM versus CCM (including data for 15 mmol/L LA vs. Veh – H<sub>2</sub>O) within ”fatty acid metabolism”. <b>C,</b> Significant intracellular (<i>P</i> < 0.05) metabolites in FRCs treated for 4 days with B16.F10 TCM versus CCM <i>in vitro</i>, measured by LC–MS and normalized on protein level. <b>D,</b> Significant intracellular (<i>P</i> < 0.05) metabolites in FRCs treated for 4 days with 15 mmol/L LA versus Veh – H<sub>2</sub>O <i>in vitro</i>, measured by LC–MS and normalized on cell number. <b>E,</b> Relative intracellular glutathione levels in FRCs treated for 4 days with CCM, B16.F10 TCM, 4T1 TCM, 15 mmol/L LA, or Veh – H<sub>2</sub>O <i>in vitro</i>, measured by LC–MS. <i>n</i> = 3 independent experiments. <b>F,</b> Relative abundance of citrate in brachial lymph nodes of female sham-treated (braLNs) and B16.F10 tumor-bearing C57BL/6 mice (B16 braTDLN), quantified by LC–MS. <i>n</i> = 7 independent experiments.<b>G,</b> Experimental set-up for labeling experiment. 4T1 tumor cells were cultured in <sup>13</sup>C<sub>6</sub>-glucose medium for 24 hours before medium was transferred to FRCs. In parallel, FRCs were cultured with <sup>13</sup>C<sub>3</sub> LA directly. In both cases, FRCs were treated for 4 days and metabolites measured by LC–MS. <b>H–J,</b><sup>13</sup>C-labeled metabolites identified by LC–MS using the set-up in <b>G</b>. <b>H,</b> glucose, glucose-6-P, lactate, and pyruvate. <b>I,</b> acetylcarnitine and <b>J,</b> citrate, aconitate, a-ketoglutarate, glutamate, succinate, fumarate, and malate. All <i>n</i> = 3 technical replicates. “M + n”, molecular mass plus the number of incorporated heavy carbons. Data are mean with SD. <b>K,</b> Diagram showing incorporation of lactate and pyruvate into downstream metabolites. Data are mean with SEM (unless stated differently). Significance (*, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.001; and ****, <i>P</i> < 0.0001) was determined by unpaired two-tailed <i>t</i> test. B16, B16.F10; h, hours; LA, lactic acid.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_108fc1983e5960462ed6fb4f950b86a9 |
| identifier_str_mv | 10.1158/2326-6066.30710353 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30710353 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY |
| spelling | Figure 4 from Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node StromaAngela Riedel (15130557)Moutaz Helal (15130560)Luisa Pedro (15130563)Jonathan J. Swietlik (15130566)David Shorthouse (2733004)Werner Schmitz (15130569)Lisa Haas (15130572)Timothy Young (15130575)Ana S.H. da Costa (15130578)Sarah Davidson (8254992)Pranjali Bhandare (13789834)Elmar Wolf (14952454)Benjamin A. Hall (199856)Christian Frezza (15130581)Thordur Oskarsson (2313193)Jacqueline D. Shields (14889899)CancerTumor BiologyMolecular and Cellular BiologyImmuno-oncologyImmunologyImmune responses to cancerMetabolismMitochondrial functionProgression, Invasion & MetastasisMetastasisTumor MicroenvironmentTumor-stromal cell interactions<p>Deregulated metabolism in response to tumor factors and LA. <b>A,</b> Using the RNA-seq data from <a href="#fig3" target="_blank">Fig. 3</a>, depicted here are the top 10 most significant GO terms for ”biological process” using all significantly upregulated genes in <i>in vitro</i> cultured FRCs treated for 4 days with B16.F10 TCM versus CCM. <b>B,</b> Heatmap displaying significant deregulated genes in TCM versus CCM (including data for 15 mmol/L LA vs. Veh – H<sub>2</sub>O) within ”fatty acid metabolism”. <b>C,</b> Significant intracellular (<i>P</i> < 0.05) metabolites in FRCs treated for 4 days with B16.F10 TCM versus CCM <i>in vitro</i>, measured by LC–MS and normalized on protein level. <b>D,</b> Significant intracellular (<i>P</i> < 0.05) metabolites in FRCs treated for 4 days with 15 mmol/L LA versus Veh – H<sub>2</sub>O <i>in vitro</i>, measured by LC–MS and normalized on cell number. <b>E,</b> Relative intracellular glutathione levels in FRCs treated for 4 days with CCM, B16.F10 TCM, 4T1 TCM, 15 mmol/L LA, or Veh – H<sub>2</sub>O <i>in vitro</i>, measured by LC–MS. <i>n</i> = 3 independent experiments. <b>F,</b> Relative abundance of citrate in brachial lymph nodes of female sham-treated (braLNs) and B16.F10 tumor-bearing C57BL/6 mice (B16 braTDLN), quantified by LC–MS. <i>n</i> = 7 independent experiments.<b>G,</b> Experimental set-up for labeling experiment. 4T1 tumor cells were cultured in <sup>13</sup>C<sub>6</sub>-glucose medium for 24 hours before medium was transferred to FRCs. In parallel, FRCs were cultured with <sup>13</sup>C<sub>3</sub> LA directly. In both cases, FRCs were treated for 4 days and metabolites measured by LC–MS. <b>H–J,</b><sup>13</sup>C-labeled metabolites identified by LC–MS using the set-up in <b>G</b>. <b>H,</b> glucose, glucose-6-P, lactate, and pyruvate. <b>I,</b> acetylcarnitine and <b>J,</b> citrate, aconitate, a-ketoglutarate, glutamate, succinate, fumarate, and malate. All <i>n</i> = 3 technical replicates. “M + n”, molecular mass plus the number of incorporated heavy carbons. Data are mean with SD. <b>K,</b> Diagram showing incorporation of lactate and pyruvate into downstream metabolites. Data are mean with SEM (unless stated differently). Significance (*, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.001; and ****, <i>P</i> < 0.0001) was determined by unpaired two-tailed <i>t</i> test. B16, B16.F10; h, hours; LA, lactic acid.</p>2025-11-25T13:44:07ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.1158/2326-6066.30710353https://figshare.com/articles/figure/Figure_4_from_Tumor-Derived_Lactic_Acid_Modulates_Activation_and_Metabolic_Status_of_Draining_Lymph_Node_Stroma/30710353CC BYinfo:eu-repo/semantics/openAccessoai:figshare.com:article/307103532025-11-25T13:44:07Z |
| spellingShingle | Figure 4 from Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node Stroma Angela Riedel (15130557) Cancer Tumor Biology Molecular and Cellular Biology Immuno-oncology Immunology Immune responses to cancer Metabolism Mitochondrial function Progression, Invasion & Metastasis Metastasis Tumor Microenvironment Tumor-stromal cell interactions |
| status_str | publishedVersion |
| title | Figure 4 from Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node Stroma |
| title_full | Figure 4 from Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node Stroma |
| title_fullStr | Figure 4 from Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node Stroma |
| title_full_unstemmed | Figure 4 from Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node Stroma |
| title_short | Figure 4 from Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node Stroma |
| title_sort | Figure 4 from Tumor-Derived Lactic Acid Modulates Activation and Metabolic Status of Draining Lymph Node Stroma |
| topic | Cancer Tumor Biology Molecular and Cellular Biology Immuno-oncology Immunology Immune responses to cancer Metabolism Mitochondrial function Progression, Invasion & Metastasis Metastasis Tumor Microenvironment Tumor-stromal cell interactions |