Breast Cancer Remodels Lymphatics in Sentinel Lymph Nodes
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PROVIDER: PRJNA1271534 | ENA |
REPOSITORIES: ENA
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Project description:Breast cancer remodels lymphatics in sentinel lymph nodes
| PRJNA1042832 | ENA
Project description:Breast cancer remodels lymphatics in sentinel lymph nodes
| PRJNA1041730 | ENA
Project description:Cancer metastasis into sentinel lymph nodes (LNs) is a crucial determinant of patient mortality. While it is recognized that tumor-induced lymphangiogenesis facilitates metastasis into LNs in murine models, the tumor-induced alterations in human lymphatic vessels remain obscure. Here we utilized single-cell RNA-seq to profile lymphatic endothelial cell (LEC) subsets in paired metastatic and non-metastatic LNs obtained from breast cancer patients. Tumor metastasis leads to a decrease in inflammatory LEC subsets such as subcapsular sinus LECs, while inducing increase of immunosuppressive CD200+ LECs. Matrix Gla protein (MGP) was the most upregulated gene in metastatic LN LECs, and its expression on LECs was VEGF and TGF-b dependent. Silencing MGP in LECs revealed that MGP promotes cancer cell adhesion to LECs. Thus, breast cancer cell metastasis into LNs remodels LEC subsets in human LNs and escalates MGP expression, which potentially facilitates the dissemination of cancer cells through lymphatics.
2025-09-01 | GSE248214 | GEO
Project description:Cancer metastasis to sentinel lymph nodes (LNs) is often the first marker of potential disease progression. Although it is recognized that tumor-induced lymphangiogenesis facilitates metastasis into LNs in murine models, tumor-induced alterations in human lymphatic vessels remain obscure. We used single-cell RNA sequencing and high-resolution spatial transcriptomics to profile lymphatic endothelial cell (LEC) subsets in paired metastatic and non-metastatic LNs obtained from patients with treatment-naïve breast cancer. Tumor metastasis decreases immunoregulatory LEC subsets, such as PD-L1+ subcapsular sinus LECs, while inducing an increase in capillary-like CD200+ HEY1+ LECs. Matrix Gla protein (MGP) was the most upregulated gene in metastatic LN LECs, and its expression on LECs was TGF-b and VEGF dependent. Upregulated MGP promotes cancer cell adhesion to LN lymphatics. Thus, breast cancer cell metastasis to LNs remodels LEC subsets in human LNs and escalates MGP expression, potentially facilitating cancer cell dissemination through the lymphatic system.
2025-09-02 | GSE298872 | GEO
Project description:In this study we investigated the effects of breast cancer cell conditioned media on human lymphatic endothlial cells. For this, we cultured the three different breast cancer cell lines MDA-MB-231, MCF-7 and T47D in endothelial cell media and transferred this conditioned media to primary, lymph-node derived human lymphatic endothelial cells. These cells were then collected and RNA-sequencing was performed from them.
2025-09-01 | GSE248076 | GEO
Project description:Background Breast cancer patients who present in the early stage of disease are affected by metastasis to the axillary group of lymph nodes. The first among this group that is affected is called as sentinel lymph node, and metastasis to this lymph node is crucial for the staging of cancer and the quality of surgical intervention. Sentinel Lymph Node Biopsy (SLNB) that is currently used to assess lymph node metastasis is neither sensitive, nor specific, is time-consuming, thereby necessitating the identification of novel biomarkers that can flag sentinel lymph node metastasis. Methods Breast cancer patients were screened, and those with early stage were recruited in the study. Surgical resection of the breast was followed by identification of sentinel lymph nodes by methylene fluorescent technique. Histo-pathology of fresh frozen section biopsy was used as the gold standard to assign the clinical phenotypes of metastatic (SLNM+) and non-metastatic sentinel lymph nodes (SLNM-). Discovery phase of the experiment included isobaric Tags for Relative and Absolute Quantitation (iTRAQ) technique comprising of six comparative experiments coupled with mass spectrometric analysis on Orbitrap Fusion to identify differentially expressed proteins on Proteome Discoverer 2.4. Functional enrichment and pathway analyses of differentially regulated genes was carried out in DAVID functional annotation tool. Validation was done by ELISA and protein concentrations were used to estimate the ROC for computing diagnostic parameters. Results Based on MS/MS spectra there were 2396 unique protein groups and 81 differentially expressed proteins comparing SLNB + and SLNB -. Nineteen proteins up-regulated, and eight proteins that were down regulated in SLNB+ as compared to SLNB-. Bioinformatic analysis showed the implication of extra cellular matrix proteins and ECM-receptor interaction pathways to be implicated in lymph node metastasis. ELISA confirmed the up-regulation of caveolin 1, collagen α-1, desmin, fibrillin-1, and microfibrillar associated glycoprotein 4 in metastatic, as compared to non-metastatic lymph nodes. These proteins are known to be integral in tumorogenesis, cell proliferation, invasion, cell survival and anti-apoptosis. These proteins have 80%-100%, of sensitivity and specificity to differentiate the two clinical phenotypes. Conclusion Identified extra cellular matrix protein biomarkers have requisite diagnostic parameters to be developed as a translational tool to assess the status of sentinel lymph nodes during mastectomy procedure to guide surgical therapy of axillary lymph nodes in early breast oncology.
2022-05-01 | PXD027668 | Pride
Project description:Cutaneous melanoma first metastasizes into sentinel lymph nodes that control the lymphatic drain from the area of the primary tumor. This observation is used clinically for melanoma patients with primary melanomas thicker than 1mm (tumor stage ≥T2a), for these patients sentinel lymph node biopsy has become an important and routinely performed diagnostic procedure. The importance of sentinel node analysis is reflected by a significant better prognosis of melanoma patients with tumor free sentinel nodes compared to patients with metastatic sentinel nodes. Although intensively studied, not much is known about mechanisms responsible for the development of melanoma metastasis.To analyze gene expression in mouse SLNs of M24met tumor bearing animals as compared to tumor free control animals, SLNs were taken at different time points and analyzed for the presence of human M24met to classify SLNs into control, negative, macro metastatic SLN. After categorized SLNs were subjected to microarray analysis.
2011-07-15 | GSE30688 | GEO
Project description:Cutaneous melanoma first metastasizes into sentinel lymph nodes that control the lymphatic drain from the area of the primary tumor. This observation is used clinically for melanoma patients with primary melanomas thicker than 1mm (tumor stage ≥T2a), for these patients sentinel lymph node biopsy has become an important and routinely performed diagnostic procedure. The importance of sentinel node analysis is reflected by a significant better prognosis of melanoma patients with tumor free sentinel nodes compared to patients with metastatic sentinel nodes. Although intensively studied, not much is known about mechanisms responsible for the development of melanoma metastasis.To analyze gene expression in mouse SLNs of M24met tumor bearing animals as compared to tumor free control animals, SLNs were taken at different time points and analyzed for the presence of human M24met to classify SLNs into control, negative, macro metastatic SLN. After categorized SLNs were subjected to microarray analysis. To analyze gene expression in mouse SLNs of human M24met tumor bearing animals as compared to tumor free control animals, SLNs were taken at different time points and analyzed for the presence of human M24met to classify SLNs into control, negative, macro metastatic SLN. Briefly, explanted SLNs were stored in RNA later (Ambion, Austin, TX) and DNA as well as RNA was extracted using AllPrep DNA/RNA Mini Kit and RNeasy Micro Kit (Qiagen, Valencia, CA) according to manufacturer’s instructions. To detect human cells in mouse SLNs we used a polymerase chain reaction method for the detection of a human-specific 850-bp fragment of the alpha-satellite DNA on human chromosome 17. For analysis of gene expression RNA from control SLN from tumor free animals (control), RNA from tumor negative SLN (negative), and RNA from macro metastatic SLN (positive) from tumor bearing animals was used to analyze gene expression on Mouse Genome 430A 2.0 Arrays (Affymetrix, Santa Clara, CA)
2011-07-14 | E-GEOD-30688 | biostudies-arrayexpress
Project description:We analyzed the expression of multiple genes involved in immunosuppressive and exhaustion pathways in sentinel lymph nodes (sLN) isolated from mice previously depleted of macrophages (CLL treated) and we compared them with non-depleted animals.
2022-08-25 | GSE208247 | GEO
Project description:Surgical ablation or radiation of tumor-draining lymph nodes can eliminate the primary tumor response to immunotherapy, indicating that local tumor response to immunotherapy is mediated by tumor-draining lymph nodes. Here, we show that immunoradiotherapy efficacy is dependent on immune cell migration from tumor to sentinel lymph nodes. Using a tamoxifen-inducible reporter paired with CITE-sequencing in a murine model of oral cancer, we characterized tumor immune cellular migration through lymphatic channels to sentinel lymph nodes at single-cell resolution. Within a structured approach of sequential immunomodulatory radiotherapy and checkpoint inhibition, we demonstrate that lymphatic-sparing, tumor-directed radiotherapy followed by PD-1 inhibition achieves complete and durable tumor responses. Mechanistically, this treatment approach enhances activated, migratory CCR7+ dendritic cell surveillance across the tumor-sentinel lymph node axis, revealing a shift from their canonical role in promoting tolerance to driving antitumor immunity. Overall, this work supports rationally sequencing immune-sensitizing, lymphatic-preserving, tumor-directed radiotherapy followed by immune checkpoint inhibition to optimize the tumor response. By characterizing the tumor-sentinel lymph node immunomigratome that drives durable antitumor response, we reveal a therapeutic opportunity to enhance the response to immunotherapy by optimizing activated dendritic cell migration to tumor-draining sentinel nodes.
2025-06-07 | GSE276437 | GEO