Cell migration is a critical event in many physiological processes, such as embryogenesis, inflammation, and tissue regeneration, as well as malignant states, such as cancer metastasis. Cells migrate in response to gradients of chemical factors (chemotaxis ), gravitational forces (geotaxis), and electrostatic potentials (galvanotaxis). Recently, cells were found to directionally migrate also in response to gradients of substrate rigidity (mechanotaxis). Thus far, cell types that are exposed to or depend on constant fluctuations of the mechanical properties of their microenvironment, such as osteoclasts, smooth muscle cells, and endothelial cells, exhibit mechanotaxis. Increased rigidity is a strong characteristic of solid tumours. Invasive cancer cells are subject to alterations in the mechanical properties of the primary tumour microenvironment they originate from, as well as the tissue where they metastasize. Nonetheless, mechanotaxis and its controlling mechanisms have barely been studied for cancer cells.
The goals of the proposed project are to:
a) determine whether various human cancer cell lines, initially, and primary cancer cells, subsequently, of varying invasiveness exhibit mechanotaxis on two and three dimensional substrates of different rigidities;
b) investigate the intracellular signalling pathways directing mechanotaxis in metastatic cancer cells; and
c) study cancer cell migration in response to parallel or opposing gradients of both mechanical (mechanotaxis) and chemical (chemotaxis) stimuli.
Collaboration with scientists from other disciplines (biomathematics and physics) will enable the compilation of the biological results into mathematical models that can be employed in the prediction of the course of metastasis. The gained knowledge from this project will further our understanding on the tissue microenvironment cues that metastatic cells are prone to respond to, thus providing a potential new tool in the prevention or inhibition of metastasis.
Call for proposal
See other projects for this call