The characteristics of Ishikawa endometrial cancer cells are modified by substrate topography with cell-like features and the polymer surface.
Conventional in vitro culture studies on flat surfaces do not reproduce tissue environments, which have inherent topographical mechanical signals. To understand the impact of these mechanical signals better, we use a cell imprinting technique to replicate cell features onto hard polymer culture surfaces as an alternative platform for investigating biomechanical effects on cells; the high-resolution replication of cells offers the micro- and nanotopography experienced in typical cell-cell interactions. We call this platform a Bioimprint. Cells of an endometrial adenocarcinoma cell line, Ishikawa, were cultured on a bioimprinted substrate, in which Ishikawa cells were replicated on polymethacrylate (pMA) and polystyrene (pST), and compared to cells cultured on flat surfaces. Characteristics of cells, incorporating morphology and cell responses, including expression of adhesion-associated molecules and cell proliferation, were studied. In this project, we fabricated two different topographies for the cells to grow on: a negative imprint that creates cell-shaped hollows and a positive imprint that recreates the raised surface topography of a cell layer. We used two different substrate materials, pMA and pST. We observed that cells on imprinted substrates of both polymers, compared to cells on flat surfaces, exhibited higher expression of β1-integrin, focal adhesion kinase, and cytokeratin-18. Compared to cells on flat surfaces, cells were larger on imprinted pMA and more in number, whereas on pST-imprinted surfaces, cells were smaller and fewer than those on a flat pST surface. This method, which provided substrates in vitro with cell-like features, enabled the study of effects of topographies that are similar to those experienced by cells in vivo. The observations establish that such a physical environment has an effect on cancer cell behavior independent of the characteristics of the substrate. The results support the concept that the physical topography of a cell's environment may modulate crucial oncological signaling pathways; this suggests the possibility of cancer therapies that target pathways associated with the response to mechanical stimuli.
Department of Obstetrics and Gynaecology, University of Otago, Christchurch, New Zealand ; MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New Zealand.
Li Hui
LH
Tan
Department of Obstetrics and Gynaecology, University of Otago, Christchurch, New Zealand.
Peter H
PH
Sykes
MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New Zealand ; Department of Electrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand.
Maan M
MM
Alkaisi
Department of Obstetrics and Gynaecology, University of Otago, Christchurch, New Zealand ; MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New Zealand ; Centre for Neuroendocrinology, University of Otago, Christchurch, New Zealand.
John J
JJ
Evans
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D001696:Biomechanical Phenomena; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D053538:Keratin-18 / Q000378:metabolism; D051379:Mice; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D013499:Surface Properties
D019012:Integrin beta1; C488421:KRT18 protein, human; D053538:Keratin-18; D011108:Polymers; D011109:Polymethacrylic Acids; D011137:Polystyrenes; C030613:polymethacrylic acid; D051416:Focal Adhesion Protein-Tyrosine Kinases
cell culture platforms; cell response; drug targets; mechanical forces; physical microenvironment; surface characteristics