Abstract:
:Tumor initiation and growth is associated with significant changes in the surrounding tissue. During carcinoma progression, a global stiffening of the extracellular matrix is observed and is interpreted as a signature of aggressive invasive tumors. However, it is still unknown whether this increase in matrix rigidity promotes invasion and whether this effect is constant along the course of invasion. Here we have developed a biomimetic in vitro assay that enabled us to address the question of the importance of tissue rigidity in the chronology of tumor invasion. Using low concentrations of the sugar threose, we can effectively stiffen reconstituted collagen I matrices and control the stiffening in time with no direct effect on residing cells. Our findings demonstrate that, depending on the timing of its stiffening, the extracellular matrix could either inhibit or promote cancer cell invasion and subsequent metastasis: while matrix stiffening after the onset of invasion promotes cancer cell migration and tumor spreading, stiff matrices encapsulate the tumor at an early stage and prevent cancer cell invasion. Our study suggests that adding a temporal dimension in in vitro models to analyze biological processes in four dimensions is necessary to fully capture their complexity.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Staneva R,Burla F,Koenderink GH,Descroix S,Vignjevic DM,Attieh Y,Verhulsel Mdoi
10.1091/mbc.E18-01-0068subject
Has Abstractpub_date
2018-12-01 00:00:00pages
2979-2988issue
25eissn
1059-1524issn
1939-4586journal_volume
29pub_type
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