Palladin mediates stiffness-induced fibroblast activation in the tumor microenvironment.

ABSTRACT: Mechanical properties of the tumor microenvironment have emerged as key factors in tumor progression. It has been proposed that increased tissue stiffness can transform stromal fibroblasts into carcinoma-associated fibroblasts. However, it is unclear whether the three to five times increase in stiffness seen in tumor-adjacent stroma is sufficient for fibroblast activation. In this study we developed a three-dimensional (3D) hydrogel model with precisely tunable stiffness and show that a physiologically relevant increase in stiffness is sufficient to lead to fibroblast activation. We found that soluble factors including CC-motif chemokine ligand (CCL) chemokines and fibronectin are necessary for this activation, and the combination of C-C chemokine receptor type 4 (CCR4) chemokine receptors

SUBMITTER: McLane JS 

PROVIDER: S-EPMC4621820 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature