Three-dimensional chemotaxis-driven aggregation of tumor cells

Abstract

One of the most important steps in tumor progression involves the transformation from a differentiated epithelial phenotype to an aggressive, highly motile phenotype, where tumor cells invade neighboring tissues. Invasion can occur either by isolated mesenchymal cells or by aggregates that migrate collectively and do not lose completely the epithelial phenotype. Here, we show that, in a three-dimensional cancer cell culture, collective migration of cells eventually leads to aggregation in large clusters. We present quantitative measurements of cluster velocity, coalescence rates, and proliferation rates. These results cannot be explained in terms of random aggregation. Instead, a model of chemotaxis-driven aggregation – mediated by a diffusible attractant – is able to capture several quantitative aspects of our results. Experimental assays of chemotaxis towards culture conditioned media confirm this hypothesis. Theoretical and numerical results further suggest an important role for chemotactic-driven aggregation in spreading and survival of tumor cells.

A Tumor‐on‐a‐Chip System with Bioprinted Blood and Lymphatic Vessel Pair

“…Earlier examples were primarily based on tumor spheroids, which were inadequate due to their simplicity and reproducibility [7] . More recently, tumor cells have been seeded within 3D scaffolds or matrices, and similar to an in vivo tumor, they freely extend [8] , polarize [9] , migrate, and cluster [10,11] within the matrix. Moreover, these 3D tumor models display advantages in reestablishing cell functions [12] , signaling pathways [13,14] , and drugs responses [15] as compared to traditional 2D cultivation models, hence becoming more favorable in screening of pharmaceutical compounds [16][17][18] .…”

Collective Chemotaxis through Noisy Multicellular Gradient Sensing

“…Clusters of mammary epithelial cells, lymphocytes and neural crest cells can detect chemical gradients that single cells cannot [7][8][9], and cultures of neurons have been shown to be sensitive to single molecule differences across an individual neuron's axonal growth cone [10]. In many types of cancer, tumor cell invasion is collective, involving coherent grouped motion guided by chemical cues [11][12][13][14]. It is clear from these examples that cells acting collectively can improve upon their individual sensory precision.…”

Tissue Extract Fractions from Starfish Undergoing Regeneration Promote Wound Healing and Lower Jaw Blastema Regeneration of Zebrafish

“…Although peptides30 and molecules31 have been reported to mediate cell migration and aggregation, use of an in vitro organotypic wound-healing model has revealed a paracrine signaling network containing multiple growth factors and cytokines that orchestrate cell behavioral and phenotypic changes during wound healing3233. As tissue regeneration is a complicated process involving multiple types of cells and tissues, a relatively pure mixture of bioactive extracts can better establish the micro-environmental niche and deliver construct cues.…”