Revealing the structural microenvironment of high metastatic risk uveal melanomas following decellularisation
Abstract Uveal melanoma (UM) is a rare aggressive intraocular tumour that spreads most commonly to the liver in tumours with loss of one copy of chromosome 3 (HR-M3); current treatments for metastatic disease remain largely ineffective. Pre-clinical research is increasingly using three-dimensional m...
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-78171-2 |
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| author | Karen Aughton Joshua Hattersley Sarah E Coupland Helen Kalirai |
| author_facet | Karen Aughton Joshua Hattersley Sarah E Coupland Helen Kalirai |
| author_sort | Karen Aughton |
| collection | DOAJ |
| description | Abstract Uveal melanoma (UM) is a rare aggressive intraocular tumour that spreads most commonly to the liver in tumours with loss of one copy of chromosome 3 (HR-M3); current treatments for metastatic disease remain largely ineffective. Pre-clinical research is increasingly using three-dimensional models that better recapitulate the tumour microenvironment (TME). One aspect of the TME is the acellular extracellular matrix (ECM) that influences cell proliferation, migration and response to therapy. Although commercial matrices are used in culture, the composition and biochemical properties may not be representative of the tumour ECM in vivo. This study identifies UM metastatic risk specific ECM proteins by developing methodology for decellularisation of low- and high- metastatic risk tissue samples (LR-D3 vs. HR-M3). Proteomic analysis revealed a matrisome signature of 34 core ECM and ECM-associated proteins upregulated in HR-M3 UM. Combining additional UM secretome and whole cell iTRAQ proteomic datasets revealed enriched GO and KEGG pathways including ‘regulating ECM binding’ and ‘PI3K/Akt signalling’. Structural analyses of decellularised matrices revealed microarchitecture of differing fibre density and expression differences in collagen 4, collagen 6A1 and nidogen 1, between metastatic risk groups. This approach is a powerful tool for the generation of ECM matrices relevant to high metastatic risk UM. |
| format | Article |
| id | doaj-art-d102b717b0814e5f85c61bc4532fd65f |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-d102b717b0814e5f85c61bc4532fd65f2025-08-20T02:50:00ZengNature PortfolioScientific Reports2045-23222024-11-0114111510.1038/s41598-024-78171-2Revealing the structural microenvironment of high metastatic risk uveal melanomas following decellularisationKaren Aughton0Joshua Hattersley1Sarah E Coupland2Helen Kalirai3Liverpool Ocular Oncology Research Group, Department of Eye and Vision Science, Institute of Life Course and Medical Science, University of LiverpoolLiverpool Ocular Oncology Research Group, Department of Eye and Vision Science, Institute of Life Course and Medical Science, University of LiverpoolLiverpool Ocular Oncology Research Group, Department of Eye and Vision Science, Institute of Life Course and Medical Science, University of LiverpoolLiverpool Ocular Oncology Research Group, Department of Eye and Vision Science, Institute of Life Course and Medical Science, University of LiverpoolAbstract Uveal melanoma (UM) is a rare aggressive intraocular tumour that spreads most commonly to the liver in tumours with loss of one copy of chromosome 3 (HR-M3); current treatments for metastatic disease remain largely ineffective. Pre-clinical research is increasingly using three-dimensional models that better recapitulate the tumour microenvironment (TME). One aspect of the TME is the acellular extracellular matrix (ECM) that influences cell proliferation, migration and response to therapy. Although commercial matrices are used in culture, the composition and biochemical properties may not be representative of the tumour ECM in vivo. This study identifies UM metastatic risk specific ECM proteins by developing methodology for decellularisation of low- and high- metastatic risk tissue samples (LR-D3 vs. HR-M3). Proteomic analysis revealed a matrisome signature of 34 core ECM and ECM-associated proteins upregulated in HR-M3 UM. Combining additional UM secretome and whole cell iTRAQ proteomic datasets revealed enriched GO and KEGG pathways including ‘regulating ECM binding’ and ‘PI3K/Akt signalling’. Structural analyses of decellularised matrices revealed microarchitecture of differing fibre density and expression differences in collagen 4, collagen 6A1 and nidogen 1, between metastatic risk groups. This approach is a powerful tool for the generation of ECM matrices relevant to high metastatic risk UM.https://doi.org/10.1038/s41598-024-78171-2Uveal melanomaTumour microenvironmentExtracellular matrixProteomicsMetastatic riskDecellularisation |
| spellingShingle | Karen Aughton Joshua Hattersley Sarah E Coupland Helen Kalirai Revealing the structural microenvironment of high metastatic risk uveal melanomas following decellularisation Scientific Reports Uveal melanoma Tumour microenvironment Extracellular matrix Proteomics Metastatic risk Decellularisation |
| title | Revealing the structural microenvironment of high metastatic risk uveal melanomas following decellularisation |
| title_full | Revealing the structural microenvironment of high metastatic risk uveal melanomas following decellularisation |
| title_fullStr | Revealing the structural microenvironment of high metastatic risk uveal melanomas following decellularisation |
| title_full_unstemmed | Revealing the structural microenvironment of high metastatic risk uveal melanomas following decellularisation |
| title_short | Revealing the structural microenvironment of high metastatic risk uveal melanomas following decellularisation |
| title_sort | revealing the structural microenvironment of high metastatic risk uveal melanomas following decellularisation |
| topic | Uveal melanoma Tumour microenvironment Extracellular matrix Proteomics Metastatic risk Decellularisation |
| url | https://doi.org/10.1038/s41598-024-78171-2 |
| work_keys_str_mv | AT karenaughton revealingthestructuralmicroenvironmentofhighmetastaticriskuvealmelanomasfollowingdecellularisation AT joshuahattersley revealingthestructuralmicroenvironmentofhighmetastaticriskuvealmelanomasfollowingdecellularisation AT sarahecoupland revealingthestructuralmicroenvironmentofhighmetastaticriskuvealmelanomasfollowingdecellularisation AT helenkalirai revealingthestructuralmicroenvironmentofhighmetastaticriskuvealmelanomasfollowingdecellularisation |