In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblasts

Abstract

A combination of multiphoton laser scanning microscopy and second harmonic generation (SHG) imaging is used to track tumor associated fibroblasts and extracellular matrix remodeling in living mice. The SHG signal is used for image registration over several days. Here we integrated multiphoton laser scanning microscopy and the registration of second harmonic generation images of collagen fibers to overcome difficulties in tracking stromal cell-matrix interactions for several days in live mice. We show that the matrix-modifying hormone relaxin increased tumor-associated fibroblast (TAF) interaction with collagen fibers by stimulating β1-integrin activity, which is necessary for fiber remodeling by matrix metalloproteinases.