Proteomic profiling identifies markers for inflammation-related tumor–fibroblast interaction

Clinical Proteomics

Andrea Beer¹  Zeynep N. Erdem²  Daniel Drev²  Thomas Mohr²  Gerald Timelthaler²  Brigitte Marian²  Christopher Gerner³  Andrea Bileck³ 

[1] Clinical Institute of Pathology, Medical University of Vienna;Department of Medicine 1, Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna;Institute of Analytical Chemistry, University of Vienna;

关键词: Inflammation signature;    Colorectal cancer;    Cancer associated fibroblasts;    SPARC;    THBS2;    Extracellular matrix organization;   

DOI  :  10.1186/s12014-017-9168-7

来源: DOAJ

【 摘 要 】

Abstract Background Cancer associated fibroblasts are activated in the tumor microenvironment and contribute to tumor progression, angiogenesis, extracellular matrix remodeling, and inflammation. Methods To identify proteins characteristic for fibroblasts in colorectal cancer we used liquid chromatography-tandem mass spectrometry to derive protein abundance from whole-tissue homogenates of human colorectal cancer/normal mucosa pairs. Alterations of protein levels were determined by two-sided t test with greater than threefold difference and an FDR of < 0.05. Public available datasets were used to predict proteins of stromal origin and link protein with mRNA regulation. Immunohistochemistry confirmed the localization of selected proteins. Results We identified a set of 24 proteins associated with inflammation, matrix organization, TGFβ receptor signaling and angiogenesis mainly originating from the stroma. Most prominent were increased abundance of SerpinB5 in the parenchyme and latent transforming growth factor β-binding protein, thrombospondin-B2, and secreted protein acidic-and-cysteine-rich in the stroma. Extracellular matrix remodeling involved collagens type VIII, XII, XIV, and VI as well as lysyl-oxidase-2. In silico analysis of mRNA levels demonstrated altered expression in the tumor and the adjacent normal tissue as compared to mucosa of healthy individuals indicating that inflammatory activation affected the surrounding tissue. Immunohistochemistry of 26 tumor specimen confirmed upregulation of SerpinB5, thrombospondin B2 and secreted protein acidic-and-cysteine-rich. Conclusions This study demonstrates the feasibility of detecting tumor- and compartment-specific protein-signatures that are functionally meaningful by proteomic profiling of whole-tissue extracts together with mining of RNA expression datasets. The results provide the basis for further exploration of inflammation-related stromal markers in larger patient cohorts and experimental models.

【 授权许可】

Unknown