Insights into Biochemical Alteration in Cancer-Associated Fibroblasts by using Novel Correlative Spectroscopy.
The microenvironment of a tumor changes chemically and morphologically during cancer progression. Cancer-stimulated fibroblasts promote tumor growth, however, the mechanism of the transition to a cancer-stimulated fibroblast remains elusive. Here, the multi-modal spectroscopic methods Fourier transform infrared imaging (FTIRI), X-ray absorption spectroscopy (XAS) and X-ray fluorescence imaging (XFI) are used to characterize molecular and atomic alterations that occur in cancer-stimulated fibroblasts. In addition to chemical changes in lipids (olefinic and acyl chain) and protein aggregation observed with FTIRI, a new infrared biomarker for oxidative stress in stimulated fibroblasts is reported. Oxidative stress is observed to cause lipid peroxidation, which leads to the appearance of a new band at 1721 cm-1, assigned to 4-hydroxynonenal. Complementary to FTIRI, XFI is well suited to determining atom concentrations and XAS can reveal the speciation of individual elements. XFI reveals increased concentrations of P, S, K, Ca within stimulated fibroblasts. Furthermore, XAS studies reveal alterations in the speciation of S and Ca in stimulated fibroblasts, which might provide insight into the mechanisms of cancer progression. Using XFI, not only is the concentration change of individual elements observed, but also the subcellular localization. This study demonstrates the wealth of biochemical information provided by a multi-modal imaging approach and highlights new avenues for future research into the microenvironment of breast tumors.
Berzelii Technology Centre for Neurodiagnostics Department of Engineering Science Uppsala University Uppsala 75105 Sweden; Department of Biophysics All India Institute of Medical Sciences New Delhi 110029 India; Canadian Light Source Saskatoon SK S7N 2V3 Canada.
Saroj
S
Kumar
Canadian Light Source Saskatoon SK S7N 2V3 Canada.
Xia
X
Liu
SOLEIL Synchrotron 91190 Gif-sur-Yvette Ile-de-France France.
Ferenc
F
Borondics
Canadian Light Source Saskatoon SK S7N 2V3 Canada.
Qunfeng
Q
Xiao
Canadian Light Source Saskatoon SK S7N 2V3 Canada.
Renfei
R
Feng
Structure and Function of Biological Membranes (SFMB) Université Libre de Bruxelles Belgium.
Erik
E
Goormaghtigh
Berzelii Technology Centre for Neurodiagnostics Department of Engineering Science Uppsala University Uppsala 75105 Sweden.
Fredrik
F
Nikolajeff
Fourier transform infrared imaging; X-ray absorption spectroscopy; X-ray fluorescence imaging; cancer; fibroblasts