The Migration of Cancer Cells in Gradually Varying Chemical Gradients and Mechanical Constraints

Abstract

Abstract:We report a novel approach to study cell migration under physical stresses by utilizing established growth factor chemotaxis. This was achieved by studying cell migration in response to epidermal growth factor (EGF) chemoattraction in a gradually tapered space, imposing mechanical stresses. The device consisted of two 5-mm-diameter chambers connected by ten 600 µm -long and 10 µm -high tapered microchannels. The taper region gradually changes the width of the channel. The channels tapered from 20 µm to 5 µm over a transition length of 50 µm at a distance of 250 µm from one of the chambers. The chemoattractant drove cell migration into the narrow confines of the tapered channels, while the mechanical gradient clearly altered the migration of cells. Cells traversing the channels from the wider to narrow-end and vice versa were observed using time-lapsed imaging. Our results indicated that the impact of physical stress on cell migration patterns may be cell type specific.

3D Biomimetic Chips for Cancer Cell Migration in Nanometer-Sized Spaces Using “Ship-in-a-Bottle” Femtosecond Laser Processing

“…In another study, a microfluidic device consisting of two open chambers each with a volume of 70 μL were connected by ten microchannels 10 μm high and 600 μm long, which tapered in width from 20 to 5 μm over a transition length of 50 μm. 40 Chemoattractant-driven cell migration through the narrow tapered channels showed that the physical stress on cell migration might be cell-type specific.…”

“…It has been demonstrated that cancer cells of different tissue origin exhibit motility that occurs spontaneously (in the absence of any external gradient) and that the cells show fast and persistent movement in one direction for several hours. In another study, a microfluidic device consisting of two open chambers each with a volume of 70 μL were connected by ten microchannels 10 μm high and 600 μm long, which tapered in width from 20 to 5 μm over a transition length of 50 μm . Chemoattractant-driven cell migration through the narrow tapered channels showed that the physical stress on cell migration might be cell-type specific.…”

Onco-Breastomics: An Eco-Evo-Devo Holistic Approach

“…Comparatively, BC tumorigenesis and metastasis represent a complex cascade/continuum of cells and biomarkers that comprises successively integrated populations of heterogeneous tumor cells and cancer-associated cells, interacting in a dynamic spatio-temporal fashion under specific microenvironmental conditions (Figure 2 and Table 2). Thus, akin to the species of biological communities that form a spatial continuum in a watercourse or in other ecosystem types, cancer cells should have the ability to: (i) move to more hospitable environments when local condi-tions in primary tumor sites become unfavorable, like in case of hypoxia, nutritional and thermoregulatory stress or acidic pHe, known to promote cell invasion [295]; (ii) move to minimize the cell-cell competition for local resources; (iii) move in biomolecular gradients, following directional migration patterns that may be cell type specific [296] and adjusted by different growth factors and chemokines from the primary TME [297]; (iv) don't waste effort moving in wrong directions before drifting in the correct direction; and (v) should arrive at a specific distant site in a timely manner based on chemotactic-based behavior that requires sensing, polarizations, and directional motility, emphasizing accuracy, speed and persistence [298]. Moreover, metastasis is a selective process that favors cells with higher deformability and motility [299].…”

In vitro three-dimensional cancer metastasis modeling: Past, present, and future

“…[34,[60][61][62][63][64][65] In the presence of growth factors, tumor cells display chemokinesis and cell motility is enhanced in random directions in vitro. [33,34,59,66,67] In addition to the chemokine gradient, the oxygen and cellular pH gradients are also particularly important for tumor migration. [32,68,69] Several attempts have been made to mimic the chemoattractant gradient in the 3-D in vitro microfluidic model.…”