Interfacial geometry dictates cancer cell tumorigenicity

Abstract

Within the heterogeneous architecture of tumour tissue there exists an elusive population of stem-like cells that are implicated in both recurrence and metastasis. Here, by using engineered extracellular matrices, we show that geometric features at the perimeter of tumour tissue will prime a population of cells with a stem-cell-like phenotype. These cells show characteristics of cancer stem cells in vitro, as well as enhanced tumorigenicity in murine models of primary tumour growth and pulmonary metastases. We also show that interfacial geometry modulates cell shape, adhesion through integrin α5β1, MAPK and STAT activity, and initiation of pluripotency signalling. Our results for several human cancer cell lines suggest that interfacial geometry triggers a general mechanism for the regulation of cancer-cell state. Similar to how a growing tumour can co-opt normal soluble signalling pathways, our findings demonstrate how cancer can also exploit geometry to orchestrate oncogenesis.

Effect of water-DNA interactions on elastic properties of DNA self-assembled monolayers

“…This reconfigurable elasticity could be useful in many applications, from the design of humidity responding switches or engines 37 , to controlled delivery of enzymes or chemicals encaged on DNA SAMs that can be liberated at threshold ambient conditions or surfaces with tunable Young’s modulus for the control of cell adhesion and cell mechanosensation studies 38–40 . Besides this, the presented active layer could also be used as a DNA hybridization sensor, given the unambiguous response provided by the significant change in Young’s modulus for hybridization assays at a wide range of conditions for molecular surface density and environmental humidity.…”

Combinatorial Discovery of Defined Substrates That Promote a Stem Cell State in Malignant Melanoma

“…These are markers which we have previously shown can be upregulated via discrete biophysical parameters, and which promoted greater tumorigenicity in mice. 51 Our findings suggest that certain combinations of peptides promote upregulation of these MIC markers. A full list of the peptides with their marker expression intensity scores can be found in Supplemental Table 2 (Table S2).…”

Multicellular tumor invasion and plasticity in biomimetic materials

“…88 Soft lithography was used to transfer ECM proteins in specific geometric patterns onto hydrazine-modified PA hydrogels (Figure 3C). A murine melanoma cell line was cultured on these different shapes and immunostained for putative cancer stem-like cell markers (e.g.…”

“…One advantage of engineered biomaterial platforms is their experimental accessibility relative to animal models, which is particularly useful for optical microscopy. In the publications highlighted here, fluorescence microscopy was utilized to reveal cell migration at the periphery, 87,89,109,115,117,118,150 distinct biomarker expression, 88 disorganization of epithelial architecture, 112,113,119,120,122–124 as well as coordination between tumor and stromal cells. 128–131,133 However, many of these publications utilized manual analysis of selected cells or tissues, which samples a limited subset of the population with low throughput.…”