Extracellular matrix interactions in cancer
Collagen – safeguard against cancer progression
Our previously published results demonstrated that MT1-MMP promotes tumour progression by circumventing the induction of BIK, a Bcl2 proapoptotic member, in response to three dimensional type I collagen (3D Col1), thereby preventing apoptosis of luminal type breast cancer (BC) cells. By using a kinetic transcriptomic approach, we have deciphered the molecular mechanisms implicated in this process. A bioinformatic analysis revealed that shifting the cells from 2D plastic plates to 3D Col1 gels dramatically altered key cellular functions including apoptosis, cell proliferation, RNA processing and cytoskeleton remodelling. Our data also revealed that MT1-MMP protects invasive BC cells from apoptosis through the cleavage of collagen fibres and/or the shedding of DDR1.
Maquoi E et al., 2012 ; Assent D et al., 2015
In order to further understand the safeguard function of 3D Col1 against breast cancer progression and more specifically the impact of collagen aging, a collaborative study was initiated with Prof. Hamid Morjani (University of Reims). Breast carcinoma incidence increases with age. Because of its long half life, Col1 undergoes different post-translational changes during aging, which include among others increases in advanced glycation endproducts and crosslinks levels. Altogether, our data revealed that biological collagen aging interferes with its capacity to promote apoptosis, thereby fostering the progression of breast cancer.
CAFs – accomplices in tumour progression
A number of proteinases are implicated in the pathogenic processes that occur in the coevolution of cancer cells and their microenvironment. State of theart microscopy techniques (HD Multiphoton and Super Resolution confocal microscopes and Lightsheet microscopy) associated with homemade 3D image analysis tools are used to investigate the interactions between CAFs, cancer cells and collagens fibres, with a specific emphasis on the implications of proteinases.
