The natural bone extracellular matrix provides an environment rich in both chemical and topographical cues capable of influencing and modulating cell behaviours.
Not only do constituents of the SASP interact directly with malignant keratinocytes to modulate cell behaviour but they also appear to interact with one another and with other components of the tumour microenvironment.
Topographic features can modulate cell behaviours such as proliferation, migration, differentiation and apoptosis.
In the case of circular adhesive islands, varying the size of the pattern modulates cell behaviour via changes in cell shape and their effect on the cytoskeleton and the mechano-transduction machinery [12,13].
The highly conserved and complex Wnt pathway transduces signals from the extracellular environment through transmembrane receptors and co-receptors to have an impact on cytoskeletal rearrangements and gene expression changes and thereby modulate cell behaviour.
An important challenge in liver tissue engineering is the development of bioartificial systems that are able to favour the liver reconstruction and to modulate liver cell behaviour.
Other mediators, such as IL-8 and associated inflammatory cytokines that modulate endothelial cell behaviour, will not be discussed due to their intricate relationship with the immune system of the host during tumour initiation and growth.
TGF-β1 is frequently detected in squamous cell carcinomas (Eisma et al, 1996; Akhurst and Balmain, 1999) and it is likely that, independently of tumour cell responses to classical TGF-β1 signalling, the presence of LAP in the tumour stroma may modulate malignant cell behaviour through its interaction with integrins.
The ECM has an important function in modulating immune cell behaviours such as cell proliferation, differentiation and survival, intercellular communication, and leukocyte trafficking into inflamed tissues.
Extended Data Fig. 4 Object-vector cells are distinct from other spatially modulated cell classes.
