Background: Tumorigenesis
is attributed to the interactions of
cancer cells with the tumor microenvironment through both biochemical
cues and physical stimuli. Increased matrix deposition and realignment
of the collagen fibers are detected by cancer cells, inducing epithelial-to-mesenchymal
transition, which in turn stimulates cell motility and invasiveness.
Methods: This review provides an overview of current research on the
role of the physical microenvironment in cancer invasion. This was
achieved by using a systematic approach and providing meta-analyses.
Particular focus was placed onin vitrothree-dimensional
models of epithelial cancers. We investigated questions such as the
effect of matrix stiffening, activation of stromal cells, and identified
potential advances in mechano-based therapies. Results: Meta-analysis
revealed that 64% of studies report cancer invasion promotion as stiffness
increases, while 36% report the opposite. Experimental approaches
and data interpretations were varied, each affecting the invasion
of cancer differently. Examples are the experimental timeframes used
(24 h to 21 days), the type of polymer used (24 types), and choice
of cell line (33 cell lines). The stiffness of the 3D matrices varied
from 0.5 to 300 kPa and 19% of these matrices’ stiffness were
outside commonly accepted physiological range. 100% of the studies
outside biological stiffness range (above 20 kPa) report that stiffness
does not promote cancer invasion. Conclusions: Taking this analysis
into account, we inform on the type of experimental approaches that
could be the most relevant and provide what would be a standardized
protocol and reporting strategy.