3D extracellular matrix interactions modulate tumour cell growth, invasion and angiogenesis in engineered tumour microenvironments
Taubenberger, Anna V., Bray, Laura J., Haller, Barbara, Shaposhnykov, Artem, Binner, Marcus, Freudenberg, Uwe, Guck, Jochen, & Werner, Carsten (2016) 3D extracellular matrix interactions modulate tumour cell growth, invasion and angiogenesis in engineered tumour microenvironments. Acta Biomaterialia, 36, pp. 73-85.
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Interactions between tumour cells and extracellular matrix proteins of the tumour microenvironment play crucial roles in cancer progression. So far, however, there are only a few experimental platforms available that allow us to study these interactions systematically in a mechanically defined three-dimensional (3D) context. Here, we have studied the effect of integrin binding motifs found within common extracellular matrix (ECM) proteins on 3D breast (MCF-7) and prostate (PC-3, LNCaP) cancer cell cultures, and co-cultures with endothelial and mesenchymal stromal cells. For this purpose, matrix metalloproteinase-degradable biohybrid poly(ethylene) glycol-heparin hydrogels were decorated with the peptide motifs RGD, GFOGER (collagen I), or IKVAV (laminin-111). Over 14 days, cancer spheroids of 100-200µm formed. While the morphology of poorly invasive MCF-7 and LNCaP cells was not modulated by any of the peptide motifs, the aggressive PC-3 cells exhibited an invasive morphology when cultured in hydrogels comprising IKVAV and GFOGER motifs compared to RGD motifs or nonfunctionalised controls. PC-3 (but not MCF-7 and LNCaP) cell growth and endothelial cell infiltration were also significantly enhanced in IKVAV and GFOGER presenting gels. Taken together, we have established a 3D culture model that allows for dissecting the effect of biochemical cues on processes relevant to early cancer progression. These findings provide a basis for more mechanistic studies that may further advance our understanding of how ECM modulates cancer cell invasion and how to ultimately interfere with this process.
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|Item Type:||Journal Article|
|Keywords:||Hydrogels, Breast Cancer, Prostate Cancer, Extracellular Matrix|
|Subjects:||Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300) > Biomaterials (090301)
Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300) > Biomedical Engineering not elsewhere classified (090399)
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2016 Elsevier|
|Copyright Statement:||Licensed under the Creative Commons Attribution; Non-Commercial; No-Derivatives 4.0 International. DOI: 10.1016/j.actbio.2016.03.017|
|Deposited On:||27 Apr 2016 03:08|
|Last Modified:||01 May 2016 06:22|
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