Model for advancement of mammary epithelial tumors by increased stromal collagen. Increased fibrillar collagen in the mammary stroma directly regulates the three-dimensional mechanical microenvironment of mammary epithelial cells, influencing proliferation and phenotype. In addition, increased collagen advances a feed-forward loop with fibroblasts to promote additional collagen deposition and an increased stromal/fibroblast population resulting in increased paracrine signaling to mammary epithelial cells. The net result is increased epithelial proliferation/tumor formation and a more invasive and metastatic phenotype.
Provenzano et al. BMC Medicine 2008 6:11 doi:10.1186/1741-7015-6-11