A5074887181- Sarcoma Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Tissue Engineering and Regenerative Medicine
- Cancer Cells and Metastasis
- Cardiac tumors and thrombi
- Urologic and reproductive health conditions
- Silk-based biomaterials and applications
- RNA Research and Splicing
- Vascular Tumors and Angiosarcomas
- Tumors and Oncological Cases
- Cancer-related gene regulation
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Soft tissue tumor case studies
- Cancer Diagnosis and Treatment
- Head and Neck Cancer Studies
- Molecular Biology Techniques and Applications
- Immune responses and vaccinations
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- S100 Proteins and Annexins
Institute of Cancer Research
2021-2024
MRC Laboratory for Molecular Cell Biology
2019
University College London
2019
Lymph nodes (LNs) act as filters, constantly sampling peripheral cues. This is facilitated by the conduit network, a tubular structure of aligned extracellular matrix (ECM) fibrils ensheathed fibroblastic reticular cells (FRCs). LNs undergo rapid 3- to 5-fold expansion during adaptive immune responses, but these ECM-rich structures are not permanently damaged. Whether flow or filtering function affected LN unknown. Here, we show that conduits partially disrupted acute expansion, FRC-FRC...
Abstract Soft tissue sarcomas (STS) are rare and diverse mesenchymal cancers with limited treatment options. Here we undertake comprehensive proteomic profiling of tumour specimens from 321 STS patients representing 11 histological subtypes. Within leiomyosarcomas, identify three subtypes distinct myogenesis immune features, anatomical site distribution survival outcomes. Characterisation undifferentiated pleomorphic dedifferentiated liposarcomas low infiltrating CD3 + T-lymphocyte levels...
The landscape of extracellular matrix (ECM) alterations in soft tissue sarcomas (STS) remains poorly characterized. We aimed to investigate the tumor ECM and adhesion signaling networks present STS their clinical implications. Proteomic data from 321 patients across 11 histological subtypes were analyzed define integrin networks. Subgroup analysis was performed leiomyosarcomas (LMS), dedifferentiated liposarcomas (DDLPS), undifferentiated pleomorphic (UPS). This defined subtype-specific...
High-risk soft tissue sarcomas of the extremities and trunk wall (eSTS), as defined by Sarculator nomogram, are more likely to benefit from (neo)adjuvant anthracycline-based therapy compared low/intermediate-risk patients. The biology underpinning these differential treatment outcomes remain unknown. We analysed proteomic profiles clinical 123 eSTS A Cox model for overall survival including was fitted individual data define four risk groups. DNA replication protein signature-Sarcoma...
<p>Generation and characterization of LMS ECM solution. <b>A,</b> A workflow to generate decellularized scaffolds from fresh frozen tumors by extensive washes with detergent generation solution incubating dried acidified pepsin, followed neutralization sodium hydroxide. Paired tumor solidified samples were characterized mass spectrometry. <b>B,</b> Venn diagram showing overlap matrisome protein IDs consistently detected in all samples. Identities 24 overlapping...
<p>Supplementary Figure S1. The matrisome and adhesome profiles in soft tissue sarcoma (STS).</p>
<p>Matrisome and adhesome networks in STS. <b>A,</b> Heatmap showing a similarity matrix of Pearson’s correlation coefficients for all pairwise comparisons matrisome proteins. is split into three clusters (C1, C2, C3) identified by consensus clustering analysis. <b>B,</b> Pie charts breakdown proteins within the adhesome, core matrisome, or matrisome-associated (top), class (middle) functional annotation (bottom). <b>C,</b> Selected protein–protein...
<p>Identification, biological and clinical characterization of DDLPS subgroups. <b>A,</b> Heatmap showing the supervised clustering 57 differentially expressed matrisome adhesome proteins (DEPs) uniquely upregulated in each subgroup. Black boxes indicate unique DEPs Bottom annotations key tumor patient characteristics. “*” Indicates that a feature is significantly associated with <b>B,</b> Identities subgroup are shown on right. Colored right show functional...
<p>Supplementary Figure S3. Expression of matrisome proteins in a desmoid tumour cohort (n=37) split into 3 groups based on the % content.</p>
<p>Supplementary Figure S8. Association of the proteoglycan gene expression score with survival outcomes in The Cancer Genome Atlas sarcoma (TCGA- SARC) cohort.</p>
<p>Supplementary Figure S2. Validation of MMP14 expression in undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS) by immunohistochemistry (IHC).</p>
<p>Supplementary Figure S4. Differentially expressed matrisome proteins in synovial sarcoma (SS) cases (n=42) that either received preoperative treatment or were untreated.</p>
<p>Supplementary Figure S7. Clinical characterisation of DDLPS subgroups.</p>
<p>Proteoglycan protein expression identifies a high-risk STS group. <b>A,</b> Summary of log-rank tests used to assess significant associations matrisome-related gene sets with LRFS, MFS, and OS. The scores for each patient were obtained by taking the median focusing on 10 from Molecular Signatures Database. <b>B,</b> Identities 11 proteoglycans included in proteoglycan score. <b>C,</b> Kaplan–Meier plot OS stratification combined UPS DDLPS cohort...
<p>The matrisome and adhesome landscape of soft tissue sarcomas (STS). <b>A,</b> Annotated heatmap illustrating the unsupervised clustering (Pearson’s correlation distance) 302 components in STS cohort. Top annotation panel correspond to histological subtype. The on (left) side shows proteins belonging or databases breakdown into functional classes. <b>B,</b> Heatmap showing uniquely upregulated (indicated by black boxes) subtypes (false discovery rate <0.01,...
<p>Supplementary Figure S5. Assessment of leiomyosarcoma (LMS) extracellular matrix (ECM) solution and its effects cell migration.</p>
<p>Supplemental Methods</p>
<p>Supplementary Figure S6. Identification of LCP1 as a candidate prognostic factor in LMS.</p>