Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model
[Display omitted] Osteosarcoma management continues to lack the appropriate prognostic tools to assign personalised treatment. This leaves non-responders to standard care vulnerable to recurring disease and pulmonary metastases. Developing 3D in vitro disease models to serve as a test bed for person...
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| Veröffentlicht in: | Acta biomaterialia 2019-09, Vol.96, p.247-257 |
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| creator | Pavlou, M. Shah, M. Gikas, P. Briggs, T. Roberts, S.J. Cheema, U. |
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Osteosarcoma management continues to lack the appropriate prognostic tools to assign personalised treatment. This leaves non-responders to standard care vulnerable to recurring disease and pulmonary metastases. Developing 3D in vitro disease models to serve as a test bed for personalised treatment is a promising approach to address this issue. This study describes the generation of 3D osteosarcoma models termed “tumouroids”, which are geometrically compartmentalised to reproduce the bone cancer mass and its surrounding. Although the tumour microenvironment impacts osteosarcoma in many ways, this model focussed on interrogating the influence of a biomimetic matrix on tumour cell behaviour. The 3D matrix was supplemented with the bone-marrow proteins laminin, fibronectin and NuOss® bone granules. This led to increased invasion of osteosarcoma cell aggregates from within the bone-like matrix into the surrounding acellular bone marrow-like ECM. The presence of bone granules also yielded an atypical molecular profile of osteosarcoma cells, suggesting malignant metabolic reprogramming. Changes include decreased MMP-9 (p |
| doi_str_mv | 10.1016/j.actbio.2019.07.011 |
| format | Article |
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Osteosarcoma management continues to lack the appropriate prognostic tools to assign personalised treatment. This leaves non-responders to standard care vulnerable to recurring disease and pulmonary metastases. Developing 3D in vitro disease models to serve as a test bed for personalised treatment is a promising approach to address this issue. This study describes the generation of 3D osteosarcoma models termed “tumouroids”, which are geometrically compartmentalised to reproduce the bone cancer mass and its surrounding. Although the tumour microenvironment impacts osteosarcoma in many ways, this model focussed on interrogating the influence of a biomimetic matrix on tumour cell behaviour. The 3D matrix was supplemented with the bone-marrow proteins laminin, fibronectin and NuOss® bone granules. This led to increased invasion of osteosarcoma cell aggregates from within the bone-like matrix into the surrounding acellular bone marrow-like ECM. The presence of bone granules also yielded an atypical molecular profile of osteosarcoma cells, suggesting malignant metabolic reprogramming. Changes include decreased MMP-9 (p < 0.05) and increased PTEN (p < 0.05), MCP-1 (p < 0.01) and MCT-4 (p < 0.05) gene expression. This complex 3D biomimetic composition also changed cellular responses to doxorubicin, a common chemotherapeutic agent used to treat osteosarcoma, and reproduced key issues of in vivo treatment like drug penetrance and doxorubicin-induced bone toxicity. This work highlights the importance of a biomimetic matrix in 3D osteosarcoma models for both basic and translational research.
This study describes the generation of 3D osteosarcoma models termed “tumouroids”, which are geometrically compartmentalised to reproduce the bone cancer mass and its environment. Utilising this novel model, specific parameters of osteosarcoma growth and invasion were investigated. Osteosarcoma cell lines proliferate at a slower rate, exhibit malignant metabolic reprogramming, and respond to drug intervention at lower concentrations of doxorubicin hydrochloride in matrix-complex compared to basic tumouroids. As such, this study provides evidence that the tumour microenvironment impacts osteosarcoma in many ways. The osteosarcoma tumouroid described herein may form the basis of a personalised-medicine strategy, which will allow the testing of drug effectiveness similar to that used for antibiotic selection for pathogenic bacteria.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2019.07.011</identifier><identifier>PMID: 31302294</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>3D model ; Biocompatibility ; Biomedical materials ; Biomimetic ; Biomimetics ; Bone cancer ; Bone marrow ; Bone mass ; Bone matrix ; Cell adhesion & migration ; Cell migration ; Doxorubicin ; Extracellular matrix ; Fibronectin ; Gelatinase B ; Gene expression ; Granular materials ; In vivo methods and tests ; Laminin ; Lung diseases ; Metastases ; Monocyte chemoattractant protein 1 ; Osteosarcoma ; Osteosarcoma cells ; Osteosarcoma niche ; PTEN protein ; Three dimensional models ; Toxicity ; Tumor microenvironment ; Tumors ; Tumour engineering</subject><ispartof>Acta biomaterialia, 2019-09, Vol.96, p.247-257</ispartof><rights>2019</rights><rights>Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Sep 15, 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-f709240a6f393166cee2109bd891b027752da4c4baee826e2d0ba32a204dcd9d3</citedby><cites>FETCH-LOGICAL-c473t-f709240a6f393166cee2109bd891b027752da4c4baee826e2d0ba32a204dcd9d3</cites><orcidid>0000-0002-4366-3897</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S174270611930491X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31302294$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pavlou, M.</creatorcontrib><creatorcontrib>Shah, M.</creatorcontrib><creatorcontrib>Gikas, P.</creatorcontrib><creatorcontrib>Briggs, T.</creatorcontrib><creatorcontrib>Roberts, S.J.</creatorcontrib><creatorcontrib>Cheema, U.</creatorcontrib><title>Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
Osteosarcoma management continues to lack the appropriate prognostic tools to assign personalised treatment. This leaves non-responders to standard care vulnerable to recurring disease and pulmonary metastases. Developing 3D in vitro disease models to serve as a test bed for personalised treatment is a promising approach to address this issue. This study describes the generation of 3D osteosarcoma models termed “tumouroids”, which are geometrically compartmentalised to reproduce the bone cancer mass and its surrounding. Although the tumour microenvironment impacts osteosarcoma in many ways, this model focussed on interrogating the influence of a biomimetic matrix on tumour cell behaviour. The 3D matrix was supplemented with the bone-marrow proteins laminin, fibronectin and NuOss® bone granules. This led to increased invasion of osteosarcoma cell aggregates from within the bone-like matrix into the surrounding acellular bone marrow-like ECM. The presence of bone granules also yielded an atypical molecular profile of osteosarcoma cells, suggesting malignant metabolic reprogramming. Changes include decreased MMP-9 (p < 0.05) and increased PTEN (p < 0.05), MCP-1 (p < 0.01) and MCT-4 (p < 0.05) gene expression. This complex 3D biomimetic composition also changed cellular responses to doxorubicin, a common chemotherapeutic agent used to treat osteosarcoma, and reproduced key issues of in vivo treatment like drug penetrance and doxorubicin-induced bone toxicity. This work highlights the importance of a biomimetic matrix in 3D osteosarcoma models for both basic and translational research.
This study describes the generation of 3D osteosarcoma models termed “tumouroids”, which are geometrically compartmentalised to reproduce the bone cancer mass and its environment. Utilising this novel model, specific parameters of osteosarcoma growth and invasion were investigated. Osteosarcoma cell lines proliferate at a slower rate, exhibit malignant metabolic reprogramming, and respond to drug intervention at lower concentrations of doxorubicin hydrochloride in matrix-complex compared to basic tumouroids. As such, this study provides evidence that the tumour microenvironment impacts osteosarcoma in many ways. The osteosarcoma tumouroid described herein may form the basis of a personalised-medicine strategy, which will allow the testing of drug effectiveness similar to that used for antibiotic selection for pathogenic bacteria.</description><subject>3D model</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>Biomimetic</subject><subject>Biomimetics</subject><subject>Bone cancer</subject><subject>Bone marrow</subject><subject>Bone mass</subject><subject>Bone matrix</subject><subject>Cell adhesion & migration</subject><subject>Cell migration</subject><subject>Doxorubicin</subject><subject>Extracellular matrix</subject><subject>Fibronectin</subject><subject>Gelatinase B</subject><subject>Gene expression</subject><subject>Granular materials</subject><subject>In vivo methods and tests</subject><subject>Laminin</subject><subject>Lung diseases</subject><subject>Metastases</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Osteosarcoma</subject><subject>Osteosarcoma cells</subject><subject>Osteosarcoma niche</subject><subject>PTEN protein</subject><subject>Three dimensional models</subject><subject>Toxicity</subject><subject>Tumor microenvironment</subject><subject>Tumors</subject><subject>Tumour engineering</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kU2PFCEQhonRuB_6D4wh8eKl2wJ6oLmYmNVVk032omdCQ82ESdOMQBv330tnVg8ePEHIUy9V9RDyikHPgMl3x966OoXUc2C6B9UDY0_IJRvV2KmdHJ-2uxp4p0CyC3JVyhFAjIyPz8mFYAI418MlyfelYoohYg2ORltz-EVdiqe04FILtXPFTB3OM43hkG0NaaF28dTn9UAzlgYWpKE9UvGR1jWmNXe4HMKCmNHTtOUXm1umpTF5nF-QZ3s7F3z5eF6T77efvt186e7uP3-9-XDXuUGJ2u0VaD6AlXuhBZPSIXIGevKjZhNwpXbc28ENk0UcuUTuYbKCWw6Dd157cU3ennNPOf1YsVQTQ9kmsQumtRjOdyPbSaV1Q9_8gx7bGEvrznABkoMGuVHDmXI5lZJxb045RJsfDAOzOTFHc3ZiNicGlGlOWtnrx_B1iuj_Fv2R0ID3ZwDbNn4GzKa4gItDHzK6anwK___hN7GnoCs</recordid><startdate>20190915</startdate><enddate>20190915</enddate><creator>Pavlou, M.</creator><creator>Shah, M.</creator><creator>Gikas, P.</creator><creator>Briggs, T.</creator><creator>Roberts, S.J.</creator><creator>Cheema, U.</creator><general>Elsevier Ltd</general><general>Elsevier BV</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4366-3897</orcidid></search><sort><creationdate>20190915</creationdate><title>Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model</title><author>Pavlou, M. ; Shah, M. ; Gikas, P. ; Briggs, T. ; Roberts, S.J. ; Cheema, U.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-f709240a6f393166cee2109bd891b027752da4c4baee826e2d0ba32a204dcd9d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>3D model</topic><topic>Biocompatibility</topic><topic>Biomedical materials</topic><topic>Biomimetic</topic><topic>Biomimetics</topic><topic>Bone cancer</topic><topic>Bone marrow</topic><topic>Bone mass</topic><topic>Bone matrix</topic><topic>Cell adhesion & migration</topic><topic>Cell migration</topic><topic>Doxorubicin</topic><topic>Extracellular matrix</topic><topic>Fibronectin</topic><topic>Gelatinase B</topic><topic>Gene expression</topic><topic>Granular materials</topic><topic>In vivo methods and tests</topic><topic>Laminin</topic><topic>Lung diseases</topic><topic>Metastases</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Osteosarcoma</topic><topic>Osteosarcoma cells</topic><topic>Osteosarcoma niche</topic><topic>PTEN protein</topic><topic>Three dimensional models</topic><topic>Toxicity</topic><topic>Tumor microenvironment</topic><topic>Tumors</topic><topic>Tumour engineering</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pavlou, M.</creatorcontrib><creatorcontrib>Shah, M.</creatorcontrib><creatorcontrib>Gikas, P.</creatorcontrib><creatorcontrib>Briggs, T.</creatorcontrib><creatorcontrib>Roberts, S.J.</creatorcontrib><creatorcontrib>Cheema, U.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pavlou, M.</au><au>Shah, M.</au><au>Gikas, P.</au><au>Briggs, T.</au><au>Roberts, S.J.</au><au>Cheema, U.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2019-09-15</date><risdate>2019</risdate><volume>96</volume><spage>247</spage><epage>257</epage><pages>247-257</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
Osteosarcoma management continues to lack the appropriate prognostic tools to assign personalised treatment. This leaves non-responders to standard care vulnerable to recurring disease and pulmonary metastases. Developing 3D in vitro disease models to serve as a test bed for personalised treatment is a promising approach to address this issue. This study describes the generation of 3D osteosarcoma models termed “tumouroids”, which are geometrically compartmentalised to reproduce the bone cancer mass and its surrounding. Although the tumour microenvironment impacts osteosarcoma in many ways, this model focussed on interrogating the influence of a biomimetic matrix on tumour cell behaviour. The 3D matrix was supplemented with the bone-marrow proteins laminin, fibronectin and NuOss® bone granules. This led to increased invasion of osteosarcoma cell aggregates from within the bone-like matrix into the surrounding acellular bone marrow-like ECM. The presence of bone granules also yielded an atypical molecular profile of osteosarcoma cells, suggesting malignant metabolic reprogramming. Changes include decreased MMP-9 (p < 0.05) and increased PTEN (p < 0.05), MCP-1 (p < 0.01) and MCT-4 (p < 0.05) gene expression. This complex 3D biomimetic composition also changed cellular responses to doxorubicin, a common chemotherapeutic agent used to treat osteosarcoma, and reproduced key issues of in vivo treatment like drug penetrance and doxorubicin-induced bone toxicity. This work highlights the importance of a biomimetic matrix in 3D osteosarcoma models for both basic and translational research.
This study describes the generation of 3D osteosarcoma models termed “tumouroids”, which are geometrically compartmentalised to reproduce the bone cancer mass and its environment. Utilising this novel model, specific parameters of osteosarcoma growth and invasion were investigated. Osteosarcoma cell lines proliferate at a slower rate, exhibit malignant metabolic reprogramming, and respond to drug intervention at lower concentrations of doxorubicin hydrochloride in matrix-complex compared to basic tumouroids. As such, this study provides evidence that the tumour microenvironment impacts osteosarcoma in many ways. The osteosarcoma tumouroid described herein may form the basis of a personalised-medicine strategy, which will allow the testing of drug effectiveness similar to that used for antibiotic selection for pathogenic bacteria.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>31302294</pmid><doi>10.1016/j.actbio.2019.07.011</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-4366-3897</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 3D model Biocompatibility Biomedical materials Biomimetic Biomimetics Bone cancer Bone marrow Bone mass Bone matrix Cell adhesion & migration Cell migration Doxorubicin Extracellular matrix Fibronectin Gelatinase B Gene expression Granular materials In vivo methods and tests Laminin Lung diseases Metastases Monocyte chemoattractant protein 1 Osteosarcoma Osteosarcoma cells Osteosarcoma niche PTEN protein Three dimensional models Toxicity Tumor microenvironment Tumors Tumour engineering |
| title | Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model |
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