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

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.

[1]  T. Hewitson,et al.  Drugs of the future: the hormone relaxin , 2007, Cellular and Molecular Life Sciences.

[2]  Brian Seed,et al.  Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation , 2003, Nature Medicine.

[3]  P. Zigrino,et al.  Collagen-induced proMMP-2 activation by MT1-MMP in human dermal fibroblasts and the possible role of alpha2beta1 integrins. , 2001, European journal of cell biology.

[4]  B. Hinz,et al.  Myofibroblasts and mechano-regulation of connective tissue remodelling , 2002, Nature Reviews Molecular Cell Biology.

[5]  Michael Unser,et al.  A pyramid approach to subpixel registration based on intensity , 1998, IEEE Trans. Image Process..

[6]  R. Xavier,et al.  Tumor Induction of VEGF Promoter Activity in Stromal Cells , 1998, Cell.

[7]  M. Abercrombie,et al.  The locomotion of fibroblasts in culture. I. Movements of the leading edge. , 1970, Experimental cell research.

[8]  Frederick Grinnell,et al.  Fibroblast biology in three-dimensional collagen matrices. , 2003, Trends in cell biology.

[9]  C. Halin,et al.  In vivo imaging of lymphocyte trafficking. , 2005, Annual review of cell and developmental biology.

[10]  L. Trümper,et al.  Elevated Concentrations of Serum Relaxin are Associated with Metastatic Disease in Breast Cancer Patients , 2004, Breast Cancer Research and Treatment.

[11]  Peter Friedl,et al.  Amoeboid shape change and contact guidance: T-lymphocyte crawling through fibrillar collagen is independent of matrix remodeling by MMPs and other proteases. , 2003, Blood.

[12]  Peter Friedl,et al.  Cell migration strategies in 3‐D extracellular matrix: Differences in morphology, cell matrix interactions, and integrin function , 1998, Microscopy research and technique.