دورية أكاديمية
Engineered In Vitro Tumor Model Recapitulates Molecular Signatures of Invasion in Glioblastoma.
| العنوان: | Engineered In Vitro Tumor Model Recapitulates Molecular Signatures of Invasion in Glioblastoma. |
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| المؤلفون: | Smith LJ; Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada.; Institute for Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S 3G9, Canada.; Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada., Skirzynska A; Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada.; Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada., Chin AA; Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada., Arnold AE; Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.; Department of Chemistry, University of Toronto, 80 College Street, Toronto, Ontario M5S 3H4, Canada., Kushida M; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.; Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada., Dirks PB; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.; Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada., Shoichet MS; Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada.; Institute for Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S 3G9, Canada.; Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.; Department of Chemistry, University of Toronto, 80 College Street, Toronto, Ontario M5S 3H4, Canada. |
| المصدر: | ACS materials Au [ACS Mater Au] 2023 Jul 06; Vol. 3 (5), pp. 514-527. Date of Electronic Publication: 2023 Jul 06 (Print Publication: 2023). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: ACS Publications Country of Publication: United States NLM ID: 9918300688806676 Publication Model: eCollection Cited Medium: Internet ISSN: 2694-2461 (Electronic) Linking ISSN: 26942461 NLM ISO Abbreviation: ACS Mater Au Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : ACS Publications, [2021]- |
| مستخلص: | Glioblastoma stem cells (GSCs) play an important role in the invasive nature of glioblastoma (GBM); yet, the mechanisms driving this behavior are poorly understood. To recapitulate tumor invasion in vitro, we developed a GBM tumor-mimetic hydrogel using extracellular matrix components upregulated in patients. We show that our hydrogel facilitates the infiltration of a subset of patient-derived GSCs, differentiating samples based on phenotypic invasion. Invasive GSCs are enriched for injury-responsive pathways while noninvasive GSCs are enriched for developmental pathways, reflecting established GSC stratifications. Using small molecule inhibitors, we demonstrate that the suppression of matrix metalloprotease and rho-associated protein kinase processes results in a significant reduction of cell invasion into the hydrogel, reflecting mesenchymal- and amoeboid-dependent mechanisms. Similar reduction in cell invasion was observed by siRNA knockdown of ITGB1 and FAK focal adhesion pathways. We elucidate the transcriptomic profile of cells invading in the hydrogel by performing bulk RNA sequencing of cells cultured in the hydrogel and compare these to cells cultured in conventional tissue culture polystyrene (TCP). In our 3D hydrogel cultures, invasion-related molecular signatures along with proliferation and injury response pathways are upregulated while development processes are downregulated compared to culture on 2D TCP. With this validated in vitro model, we establish a valuable tool to find therapeutic intervention strategies against cellular invasion in glioblastoma. Competing Interests: The authors declare no competing financial interest. (© 2023 The Authors. Published by American Chemical Society.) |
| تواريخ الأحداث: | Date Created: 20231213 Latest Revision: 20231213 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10510514 |
| DOI: | 10.1021/acsmaterialsau.3c00029 |
| PMID: | 38089093 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2694-2461 |
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| DOI: | 10.1021/acsmaterialsau.3c00029 |