Aims: Renal tissue is a dynamic biophysical microenvironment, regulating healthy function and influencing tumor development. Matrix remodelling is an iterative process and aberrant tissue repair is prominent in kidney fibrosis and cancer. Biomimetic 3D models recapitulating the collagen composition and mechanical fidelity of native renal tissue were developed to investigate cell-matrix interactions in renal carcinomas. Methods: Collagen I and laminin hydrogels were engineered with renal cancer cells (ACHN and 786-O), which underwent plastic compression to generate dense matrices. Mechanical properties were determined using shear rheology and qPCR determined the gene expression of matrix markers. Results: The shear modulus and phase angle of acellular dense collagen I gels (474 Pa and 10.7) are similar to human kidney samples (1410 Pa and 10.5). After 21 days, 786-O cells softened the dense matrix (∼155 Pa), with collagen IV downregulation and upregulation of matrix metalloproteinases (MMP7 and MMP8). ACHN cells were found to be less invasive and stiffened the matrix to ∼1.25 kPa, with gene upregulation of collagen IV and the cross-linking enzyme LOX. Conclusions: Renal cancer cells remodel their biophysical environment, altering the material properties of tissue stroma in 3D models. These models can generate physiologically relevant stiffness to investigate the different matrix remodelling mechanisms utilized by cancer cells.
ACS omega. 2024 Sep 28*** epublish ***
Anuja Upadhyay, Deniz Bakkalci, Auxtine Micalet, Matt Butler, Marianne Bergin, Emad Moeendarbary, Marilena Loizidou, Umber Cheema
UCL Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, Charles Bell House, 43-45 Foley Street, W1W 7TS London, United Kingdom., UCB Pharma, 216 Bath Road, SL1 3WE Slough, United Kingdom., Department of Mechanical Engineering, Roberts Building, University College London, WC1E 6BT London, United Kingdom., Division of Surgery and Interventional Science, University College London, Royal Free Campus, Rowland Hill Street, NW3 2PF London, United Kingdom.